@article{MeyerSchartl1979,
  author    = {Meyer, Manfred K. and Schartl, Manfred},
  title     = {Eine neue Xiphophorus-Art aus Vera Cruz, Mexiko : (Pisces: Poeciliidae)},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-87124},
  year      = {1979},
  abstract  = {Xiphophorus andersi n. sp. from the Rio Atoyac, Vera Cruz, Mexico is described: lang head, moderately slender body, large dark black spar at the basis of the anal fin; adult male with short sword-like caudal appendage; rip of ray 5a of gonopodium without a developed claw. Xiphophorus andersi n. sp. differs by the combination of distinct characters from all the other species of the genus known so far. The new species shows features of both the so-called platyfish species group and the so-called swordtail species group.},
  subject      = {Schwertk{\"a}rpfling},
  language  = {en}
}
@incollection{AndersSchollSchartl1979,
  author    = {Anders, F. and Scholl, E. and Schartl, Manfred},
  title     = {Xiphophorus als Modell in der Krebsforschung},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-72752},
  publisher      = {Universit{\"a}t W{\"u}rzburg},
  year      = {1979},
  abstract  = {No abstract available.},
  subject      = {Schwertk{\"a}rpfling},
  language  = {de}
}
@inproceedings{SchartlSchartlAnders1981,
  author    = {Schartl, A. and Schartl, Manfred and Anders, F.},
  title     = {Phenotypic conversion of malignant melanoma to benign melanoma and vice versa in Xiphophorus},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-86662},
  year      = {1981},
  abstract  = {No abstract available.},
  subject      = {Schwertk{\"a}rpfling},
  language  = {en}
}
@inproceedings{AndersSchollSchartl1981,
  author    = {Anders, F. and Scholl, E. and Schartl, Manfred},
  title     = {Environmental and hereditary factors in the causation of neoplasia, based on studies of the Xiphophorus fish melanoma system},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-86402},
  year      = {1981},
  abstract  = {Neoplasia in Xiphophorus can be classified into: a) a Jarge group triggered by carcinogens; b) a large group triggered by promoters; and c) a small group that develops "spontaneously" according to Mendelian Jaw. The process leading to susceptibility for neoplasia is represented by the disintegration of gene systems that normally protect the fish from neoplasia. Interpopulational arid interracial hybridization is the most effective process that Ieads to disintegration of the protective gene systems. Environmental factors may complete disintegration in somatic cells and thus may trigger neoplasia. The applications of the findings on Xiphophorus to humans are discussed.},
  subject      = {Schwertk{\"a}rpfling},
  language  = {en}
}
@inproceedings{AndersSchartlScholl1981,
  author    = {Anders, F. and Schartl, Manfred and Scholl, E.},
  title     = {Evaluation of environmental and hereditary factors in carcinogenesis, based on studies in Xiphophorus},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-72741},
  year      = {1981},
  abstract  = {Neoplasia in Xiphophorus can be classified into a) a large group that is triggered by carcinogens; b) a large group triggered by promoters; c) a small group that develops "spontaneously" following interpopulational and interracial hybridizations; and d) a small group that develops "spontaneously" following germ line mutation. The process leading to susceptibility for neoplasia is represented by the disintegration of gene systems that normally protect the fish from neoplasia. Hybridization is the most effective process that leads to disintegration of the protection gene systems. Environmental factors may complete disintegration and thus may trigger neoplasia. It is discussed whether the findings on Xiphophorus may also apply to humans.},
  subject      = {Schwertk{\"a}rpfling},
  language  = {en}
}
@article{SchartlBarnekowBaueretal.1982,
  author    = {Schartl, Manfred and Barnekow, A. and Bauer, H. and Anders, F.},
  title     = {Correlations of inheritance and expression between a tumor gene and the cellular homolog of the Rous sarcoma virus-transforming gene in Xiphophorus},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61937},
  year      = {1982},
  abstract  = {No abstract available},
  subject      = {Physiologische Chemie},
  language  = {en}
}
@article{BarnekowSchartlAndersetal.1982,
  author    = {Barnekow, A. and Schartl, Manfred and Anders, F. and Bauer, H.},
  title     = {Identification of a fish protein associated with a kinase activity and related to the Rous sarcoma virus transforming protein},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61946},
  year      = {1982},
  abstract  = {No abstract available},
  subject      = {Physiologische Chemie},
  language  = {en}
}
@article{SchartlSchartlAnders1982,
  author    = {Schartl, A. and Schartl, Manfred and Anders, F.},
  title     = {Promotion and regression of neoplasia by testosterone-promoted cell differentiation in Xiphophorus and Girardinus},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-86684},
  year      = {1982},
  abstract  = {No abstract available.},
  subject      = {Schwertk{\"a}rpfling},
  language  = {en}
}
@article{SchartlBarnekow1982,
  author    = {Schartl, Manfred and Barnekow, Angelika},
  title     = {The expression in eukaryotes of a tyrosine kinase which is reactive with pp60v-src antibodies},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-86208},
  year      = {1982},
  abstract  = {All specimens of Eumetazoa and Parazoa, ranging from mammals, birds, teleosts, sharks, lampreys, amphioxus, insects, down to sponges showed the pp60c-src associated kinase activity, indicating that c-src, which is the cellular homologue of the oncogene v-src of Rous sarcoma virus (RSV) is probably present in all multicellular animals. Protozoa and plants did not show pp60c-src: kinase activity. The degree of c-src expression depends on the taxonomic rank of the Eumetazoa tested, and is organ-specific with nervaus tissues displaying the highest kinase activities. In the central nervous system of mammals and birds we found a high c-src expression, and in that of the lampreys, amphioxus, and insects the lowest. Unexpectedly, total extracts of sponges showed an amount of pp60c-src kinase activity similar to that of brain cell extracts of mammals and birds. These findings suggest that pp60c-src is a phylogenetic old protein that might have evolved together with the multicellular organisation of Metazoa, and that might be of importance in proliferation and differentiation of nontransformed cells.},
  subject      = {Protein-Tyrosin-Kinasen},
  language  = {en}
}
@article{SchartlBarnekow1984,
  author    = {Schartl, Manfred and Barnekow, A.},
  title     = {Differential expression of the cellular src gene during vertebrate development},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61893},
  year      = {1984},
  abstract  = {No abstract available},
  subject      = {Physiologische Chemie},
  language  = {en}
}
@article{SchartlBarnekow1984,
  author    = {Schartl, Manfred and Barnekow, A.},
  title     = {Cellular src gene product detected in the freshwater sponge Spongilla lacustris},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61904},
  year      = {1984},
  abstract  = {No abstract available},
  subject      = {Physiologische Chemie},
  language  = {en}
}
@article{RiehlSchartl1984,
  author    = {Riehl, R. and Schartl, Manfred},
  title     = {A Transmission Electron Microscopical and Freeze-Etch Study of Malignant-Melanoma in Fish},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61916},
  year      = {1984},
  abstract  = {No abstract available},
  subject      = {Physiologische Chemie},
  language  = {en}
}
@article{RiehlSchartlKollinger1984,
  author    = {Riehl, R. and Schartl, Manfred and Kollinger, G.},
  title     = {Comparative studies on the ultrastructure of malignant melanoma in fish and human by freeze-etching and transmission electron microscopy},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61920},
  year      = {1984},
  abstract  = {Malignant melanomas (MM) in the fish Xiphophorus and in humans were studied both by transmission electron microscopy (TEM) and freeze-etching (FE). In both fish and human melanomas the cells show interdigitations of the,plasma membranes. The nuclei are large and lobulated and have many nuclear pores. Melanosomes are abundant and melanosome complexes ("compound melanosomes") occur regularly. Pinocytotic vesicles could be demonstrated in fish and human melanomas showing iocal differences in frequency and distribution patterns in the tumor. lntercellular junctions are lacking in MM cells from fish and humans. The FE technique showed considerable advantages in demonstrating membrane-surface peculiarities such as nuclear pores or pinocytotic vesicles. The FE replicas of fish melanomas are like those of humans. These findings may support the hypothesis that melanoma in fish and humans reflect the same biological phenomenon.},
  subject      = {Physiologische Chemie},
  language  = {en}
}
@article{MeyerSchartl1984,
  author    = {Meyer, Manfred K. and Schartl, Manfred},
  title     = {Pseudotropheus (Maylandia) hajomaylandi n. sp., a new taxon from Lake Malawi},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-70989},
  year      = {1984},
  abstract  = {Pseudotropheus hajomaylandi (loc. typ. Isle of Chisumulu, Lake Malawi) is described as a new species. It is compared with Ps. aurora, Ps. greshakei, Ps. livingstonii, Ps. lombardoi, and Ps. zebra. All these taxa, including Ps. hajomaylandi and Ps. heteropictus, are classified in the subgenus Maylandia.},
  subject      = {Buntbarsche},
  language  = {en}
}
@inproceedings{AndersSchartlBarnekow1984,
  author    = {Anders, Fritz and Schartl, Manfred and Barnekow, Angelika},
  title     = {Xiphophorus as an in vivo model for studies on oncogenes},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-86398},
  year      = {1984},
  abstract  = {The capacity of Xiphophorus to develop neoplasia can be formally assigned to a "tumor gene" (Tu), which appears to be a normal part of the genome of all individuals. The wild fish have evolved population-specific and cell type-specific systems of regulatory genes (R) for Tu that protect the fish from neoplasia. Hybridization of members of different wild populations in the laborstory followed by treatment of the hybrids with carcinogens led to disintegration of the R systems permitting excessive expression of Tu and thus resulting in neoplasia. Certain hybrids developed neoplasia even spontaneously. Observations on the genuine phenotypic effect of the derepressed Tu in the early embryo indicated an essential normal function of this oncogene in cell differentiation, proliferation and cell-cell communication. Tu appeared to be indispensable in the genome but may also be present in accessory copics. Recently, c-src, the cellular homolog of the Rous sarcoma virus oncogene v-src, was detected in Xiphophorus. The protein product of c-src, pp60c-src, was identified and then examined by its associated kinase activity. This pp60c-src was found in all individuals tested, but, depending on the genotype, its kinase activity was different. The genetic characters of c-src, such as linkage relations, dosage relations, expression, etc., correspond to those of Tu. From a systematic study which showed that pp60c-src was present in all metazoa tested ranging from mammals down to sponges, we concluded that c-src has evolved with the multicellular organization of animals. Neoplasia of animals and humans is a characteristic closely related to this evolution. Our data showed that small aquariurn fish, besides being used successfully because they are time-, space-, and money-saving systems for carcinogenicity testing, are also highly suitable for basic studies on neoplasia at the populational, morphological, developmental, cell biological, and molecular levels.},
  subject      = {Schwertk{\"a}rpfling},
  language  = {en}
}
@article{SchartlSchmidtAndersetal.1985,
  author    = {Schartl, Manfred and Schmidt, C. R. and Anders, A. and Barnekow, A.},
  title     = {Elevated expression of the cellular src gene in tumors of differing etiologies in Xiphophorus},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61889},
  year      = {1985},
  abstract  = {No abstract available},
  subject      = {Physiologische Chemie},
  language  = {en}
}
@inproceedings{RiehlSchartlAnders1985,
  author    = {Riehl, R{\"u}diger and Schartl, Manfred and Anders, Fritz},
  title     = {An ultrastructural study of melanoma in Xiphophorus},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-70978},
  year      = {1985},
  abstract  = {Melanotic melanoma (MM) of Xiphophorus (Teleostei: Poeciliidae) was studied by conventional preparations and freeze-etch preparations for electron microscopy. MM of Xiphophorus exhibits tightly packed pigment cells with prominent dendritic processes and interdigitations of their plasma membranes. The most impressive feature of MM cells is the occurrence of Iarge lobulated nuclei with numerous nuclear pores and some nuclear pockets. Abundant spheroidal or ellipsoidal melanosomes (diameter 200-650 nm) and vesicular structures are distributed throughout the cellular dendrites, whereas the perinucJear cytoplasm is free of melanosomes. A further characteristic feature of melanoma cells in fish is the occurrence of melanosome complexes (i.e., "compound melanosomes"). These melanosome complexes consist of a few to numerous melanosomes, which are enveloped by a separate rnembrane. Pinocytotic vesicles couJd be demonstrated with distinct differences in frequency and distribution patterns, indicating differences in the metabolic activities of the cells in the same melanoma. Intercellular junctions are lacking in the MM cells. The conventional TEM technique showed clear advantages in the demonstration of intemal architecture of organelles, whereas FE bad considerable potential in respect to the visualization of membrane surface specializations.},
  subject      = {Schwertk{\"a}rpfling},
  language  = {en}
}
@inproceedings{PeterSchartlAndersetal.1985,
  author    = {Peter, R. U. and Schartl, Manfred and Anders, F. and Duncker, H.-R.},
  title     = {Pigment pattern formation during embryogenesis in Xiphophorus},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-69370},
  year      = {1985},
  abstract  = {No abstract available.},
  subject      = {Schwertk{\"a}rpfling},
  language  = {en}
}
@article{AndersSchartlBarnekowetal.1985,
  author    = {Anders, F. and Schartl, Manfred and Barnekow, A. and Schmidt, C. R. and Luke, W. and Jaenel-Dess, G. and Anders, A.},
  title     = {The genes that carcinogens act upon},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-72704},
  year      = {1985},
  abstract  = {No abstract available.},
  subject      = {Onkogen},
  language  = {en}
}
@article{MauelerEigenbrodtSchartl1987,
  author    = {Maueler, W. and Eigenbrodt, E. and Schartl, Manfred},
  title     = {Intermediary metabolism of normal and tumorous tissue of Xiphophorus (Teleostei: Poeciliidae)},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61855},
  year      = {1987},
  abstract  = {No abstract available},
  subject      = {Physiologische Chemie},
  language  = {en}
}
@article{BarnekowSchartl1987,
  author    = {Barnekow, A. and Schartl, Manfred},
  title     = {Comparative studies on the src proto-oncogene and its gene product pp60\(^{c-src}\) in normal and neoplastic tissues of lower vertebrates},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61869},
  year      = {1987},
  abstract  = {No abstract available},
  subject      = {Physiologische Chemie},
  language  = {en}
}
@article{BarnekowPaulSchartl1987,
  author    = {Barnekow, A. and Paul, E. and Schartl, Manfred},
  title     = {Expression of the c-src protooncogene in human skin tumors},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61870},
  year      = {1987},
  abstract  = {No abstract available},
  subject      = {Physiologische Chemie},
  language  = {en}
}
@article{SchartlSchroeder1987,
  author    = {Schartl, Manfred and Schr{\"o}der, Johannes Horst},
  title     = {A new species of the genus Xiphophorus Heckel 1848, endemic to northern Coahuila, Mexico (Pisces: Poeciliidae)},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-87117},
  year      = {1987},
  abstract  = {Xiphophorus meyeri n. sp. is described as an endemic to Muzquiz, Coahuila, Mexico. It appears to be the northernmost species of the genus. The new species is related to X. couchianus and X. gordoni, but differs morphologically from those by dorsal fin ray number, by the expression of some gonopodial features and most markedly by the appearance of macromelanophores or tr-melanophores.},
  subject      = {Schwertkr{\"a}pfling},
  language  = {en}
}
@article{FoersterSchartl1987,
  author    = {Foerster, Wolfgang and Schartl, Manfred},
  title     = {Karyotype and isozyme patterns of five species of Aulonocara REGAN, 1922},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-86774},
  year      = {1987},
  abstract  = {No abstract available.},
  subject      = {Aulonocara},
  language  = {en}
}
@article{AdamWittbrodtTellingetal.1988,
  author    = {Adam, D. and Wittbrodt, J. and Telling, A. and Schartl, Manfred},
  title     = {RFLP for an EGF-receptor related gene associated with the melanoma oncogene locus of Xiphophorus maculatus},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61822},
  year      = {1988},
  abstract  = {No abstract available},
  subject      = {Physiologische Chemie},
  language  = {en}
}
@article{SchartlPeter1988,
  author    = {Schartl, Manfred and Peter, R. U.},
  title     = {Progressive growth of fish tumors after transplantation into thymus-aplastic (nu/nu) mice},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61833},
  year      = {1988},
  abstract  = {No abstract available},
  subject      = {Physiologische Chemie},
  language  = {en}
}
@article{Schartl1988,
  author    = {Schartl, Manfred},
  title     = {A sex chromosomal restriction-fragment-length marker linked to melanoma-determining Tu loci in Xiphophorus},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61842},
  year      = {1988},
  abstract  = {No abstract available},
  subject      = {Physiologische Chemie},
  language  = {en}
}
@article{MaeuelerRaulfSchartl1988,
  author    = {M{\"a}ueler, Winfried and Raulf, Friedrich and Schartl, Manfred},
  title     = {Expression of proto-oncogenes in embryonic, adult, and transformed tissue of Xiphophorus (Teleostei: Poeciliidae)},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-86233},
  year      = {1988},
  abstract  = {In Xiphophorus the causative, primary cellular oncogene for melanoma formation has been assigned by classical genetics to a sex-chromosomal locus, designated Tu. Activation of Tu was proposed to be the result of the elimination of Tu-specific regulatory genes which normally suppress the transforming function in the nontumorous state. In order to understand the role which known proto-oncogenes migbt play in this process, we have analysed the expression of src, erb A, erb B, ras, abl, sis and mil related genes from Xiphophorus during embryogenesis, in non-tumorous organs and in melanoma cells. For src, ras, erb B and sis a differential expression during embryogenesis and/or in normal organs was detected, with preferential expression of src in neural tissues, a high abundance of sis transcripts in an embryonal epitheloid cellline and of erbB transcripts in the head nephros. In melanoma cells ras, src and a v-erb B related gene were found to be expressed. The src gene most likely is more involved in secondary processes during tumor progression, while the expression of the v-erb B related gene might be transformation-specific because recently such a sequence was found to map to the close vicinity of the Tu-locus.},
  subject      = {Schwertk{\"a}rpfling},
  language  = {en}
}
@article{MauelerBarnekowEigenbrodtetal.1988,
  author    = {Maueler, W. and Barnekow, A. and Eigenbrodt, E. and Raulf, F. and Falk, H. F. and Telling, A. and Schartl, Manfred},
  title     = {Different regulation of oncogene expression in tumor and embryonal cells of Xiphophorus},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-86240},
  year      = {1988},
  abstract  = {Melanoma formation in the poeciliid fish Xiphophorus is mediated primarily by a cellular oncogene, designated Tu. Elimination of Tu-specific genes releases the transforming function of Tu and leads to melanoma formation. Southern blot analyses revealed a tight linkage of a v-erb B related gene to the Tu-locus and Northern blot analyses of RNA of solid melanomas indicated a coordinated deregulation and for mutational activation of several oncogenes. In order to get a better insight into the regulation of oncogene expression in normal and transformed cells of Xiphophorus, we studied the expression of Xsrc, Xras, Xmyc, Xerb A, Xsis, and the v-erb B related gene in a melanoma derived cell line (PSM) and an embryonic cell line (A2) under conditions of low growth factor supply. Both celllines express the Xsrc, Xmyc, and Xras genes, while PSM cells in addition express the v-erb B related gene and A2 cells the Xsis gene. In PSM cells serum deprivation leads to an accumulation of most of the oncogene mRNAs analysed. This is most apparent for a 5.0 kb transcript of the v-erb B related gene, probably due to an increase in transcript stability. The levels of these mRNAs returned to normal within 2h after stimulation with 10\% fetal calf serum. At the protein level we observed an initial decrease followed by an increase of the n-p60c-src kinase (the protein product of tbe Xsrc gene) activity in cells deprived of serum. Serum stimulation restored a normal pp60"-src kinase activity. In contrast serum deprivation of A2 cells reduced the transcript amounts of each of the oncogenes analysed. The same holds true for one beta-tubulin transcript, while the level of a second beta-tubulin transcript was unaffected. Serum stimulation led to a reactivation of Xras and Xsrc after a delay of approximately 48b. The pp60(c-src) kinase activity was found to be 6-10 times lower as compared to the PSM cells and did not differ between serum deprived and serum stimulated cells. Enzyme activities and isoenzyme patterns of several glycolytic enzymes were found to be not affected by serum deprivation and stimulation in both celllines.},
  subject      = {Schwertk{\"a}rpfling},
  language  = {en}
}
@inproceedings{SchartlMaeuelerRaulfetal.1988,
  author    = {Schartl, Manfred and M{\"a}ueler, Winfried and Raulf, Friedrich and Robertson, Scott M.},
  title     = {Molecular aspects of melanoma formation in Xiphophorus},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-72689},
  year      = {1988},
  abstract  = {No abstract available.},
  subject      = {Schwertk{\"a}rpfling},
  language  = {en}
}
@article{RaulfRobertsonSchartl1989,
  author    = {Raulf, F. and Robertson, S. M. and Schartl, Manfred},
  title     = {Evolution of the neuron-specific alternative splicing product of the c-src proto-oncogene},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61796},
  year      = {1989},
  abstract  = {The observation of a slower migrating form of pp6oc-src in neural tissue of chicken and mouse has recently been shown to be due to an alternative transcript form of tbe c-src gene (Martinez et al.: Science 237:411-415, 1987; Levy et al.: Mol Cell Bio17:4142- 4145, 1987). An insertion of 18 basepairs between exons 3 and 4, presumed to be due to alternative splicing of a mini-exon, gives rise to six amino acid residues not found in the non-neuronal (termed flbroblastic) form of pp60\(^{c-src}\). Wehave addressed the question of the evolutionary origin of the c-src neuronal insert · and its functional signiflcance regarding neural-speciflc expression of the c-src gene. To this end we have investigated whether the c-src gene of a lower verlebrate (the teleost fish Xiphophorus) gives rise to a neural-specific transcript in an analogous manner. We could show that the fish c-src gene does encode for a "fibroblastic" and a "neuronal" form of transcript and that the neuronal transcript does indeed arise by way of alternative splicing of a mini-exon. The miniexon is also 18 basepairs long and we could demoostrate directly that this exon lies within the intron separating exons 3 and 4. For comparative purposes we have examined whether the fish c-yes gene, the member of the src gene family most closely related to c-src, also encodes a neural tissue-specific transcript. No evidence for a second transcript form in brain was obtained. This result suggests that the mini-exon arose within the c-src gene lineage sometime between the srclyes gene duplication event and the divergence of the evolutionary lineage giving rise to the teleost fish. Published genomic sequence of src-related genes in Drosophila and our own results with Hydra demoostrate no intron in these species at the analogous location, consistent with first appearance of this mini-exon sometime between 550 and 400 million years ago.},
  subject      = {Physiologische Chemie},
  language  = {en}
}
@article{WittbrodtAdamMalitscheketal.1989,
  author    = {Wittbrodt, J. and Adam, D. and Malitschek, B. and Maueler, W. and Raulf, F. and Telling, A. and Robertson, M. and Schartl, Manfred},
  title     = {Novel putative receptor tyrosine kinase encoded by the melanoma-inducing Tu locus in Xiphophorus},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61800},
  year      = {1989},
  abstract  = {No abstract available},
  subject      = {Physiologische Chemie},
  language  = {en}
}
@article{BernardsSchacklefordGerberetal.1989,
  author    = {Bernards, R. and Schackleford, G. M. and Gerber, M. R. and Horowitz, J. M. and Friend, S. H. and Schartl, Manfred and Bogenmann, E. and Rapaport, J. M. and Mcgee, T. and Dryja, T. P.},
  title     = {Structure and expression of the murine retinoblastoma gene and characterization of its encoded protein},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61819},
  year      = {1989},
  abstract  = {No abstract available},
  subject      = {Physiologische Chemie},
  language  = {en}
}
@article{RaulfMaeuelerRobertsonetal.1989,
  author    = {Raulf, Friedrich and M{\"a}ueler, Winfried and Robertson, Scott M. and Schartl, Manfred},
  title     = {Localization of cellular src mRNA during development and in the differentiated bipolar neurons of the adult neural retina in Xiphophorus},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-86703},
  year      = {1989},
  abstract  = {The expression of the c-src gene in embryonie and adult tissue of the teleost fish Xiphophorus helleri was analyzed by in-situ hybridization. The highly conserved fish c-src gene was found to be expressed at high levels in midterm embryos, where c-src mRNA was localized in developing neurons of the sensory layer of the differentiating retina and in the developing brain. In adult tissues the expression of c-src was found to persist in certain cell types of the brain and the neural retina, especially in the bipolar cells of the inner nuclear layer, which are postmitotic, fully differentiated mature neurons. Thus c-src in Xiphophorus appears to be a developmentally regulated proto-oncogene which is important for neuronal differentiation during organogenesis, but whose persistence of expression in certain terminally differentiated neurons strongly suggests a particular maintenance function for c-src in these cells as well.},
  subject      = {Schwertk{\"a}rpfling},
  language  = {en}
}
@article{SchartlHolsteinRobertsonetal.1989,
  author    = {Schartl, Manfred and Holstein, Thomas and Robertson, Scott M. and Barnekow, Angelika},
  title     = {Preferential expression of a pp60c-src related protein tyrosine kinase activity in nerve cells of the early metazoan Hydra (Coelenterates)},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-86179},
  year      = {1989},
  abstract  = {It has been suggested that the proto-oncogene c-src plays a functional role in developing neurons, and in the mature nerve cells of higher vertebrales. The coelenterate Hydra represents tbe most primitive known organism possessing nerve cells. With Southern blot hybridizations we have demonstrated src-related sequences in Hydra. Antisera specific for the c-src gene product (pp60 c-src) of birds and mammals precipitate a protein from Hydra cell extracts with a tyrosine-specific protein kinase activity. Studies of tissues and cells fractionated from a temperature sensitive mutant of Hydra which is depleted of interstitial (including nerve) cells at tbe non-permissive temperature, have indicated the src-like kinase of Hydra to be preferentially expressed in nerve cells. The high conservation of structural features and of the expression pattern indicates a basic function for pp60c-src in neurons.},
  subject      = {Protein-Tyrosin-Kinasen},
  language  = {en}
}
@article{Schartl1990,
  author    = {Schartl, Manfred},
  title     = {Homology of melanoma-inducing loci in the genus Xiphophorus},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61757},
  year      = {1990},
  abstract  = {Several species of the genus Xiphophorus are polymorphic for specific pigment patterns. Same of these give rise to malignant melanoma following the appropriate crossings. For one of these pattern Iod from the platyfish Xiphophorus maculatus the melanoma-inducing gene has been doned and found to encode a novel receptor tyrosine kinase, designated Xmrk. Using molecular probes from this gene in Southern blot analyses on single fish DNA preparations from 600 specimens of different populations of various species of the genus Xiphophorus and their hybrids, either with or without melanomapredisposing pattern, it was shown that all individuals contain the Xmrk gene as a proto-oncogene. It is located on the sex chromosome. All fish that carry a melanoma-predisposing locus which has been identified by Mendelian genetics contain an additional copy of Xmrk, closely linked to a specific melanophore pattern locus on the sex chromosome. The melanoma-inducing loci of the different species and populations are homologous. The additional copy of Xmrk obviously arose by a geneduplication event, thereby acquiring the oncogenic potential. The homology of the melanomainducing Iod points to a similar mechanism of tumor suppression in all feral fish populations of the different species of the genus Xiphophorus.},
  subject      = {Physiologische Chemie},
  language  = {en}
}
@article{DracopoliFeltquateSametal.1990,
  author    = {Dracopoli, Nicholas C. and Feltquate, David M. and Sam, Brigitta and Schartl, Manfred},
  title     = {Taql and Mspl RFLPs are detected by the human 2,3-biphosphoglycerate mutase (BPGM) cDNA},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61763},
  year      = {1990},
  abstract  = {No abstract available},
  subject      = {Physiologische Chemie},
  language  = {en}
}
@article{FriedenreichSchartl1990,
  author    = {Friedenreich, Hildegard and Schartl, Manfred},
  title     = {Transient expression directed by homologous and heterologous promoter and enhancer sequences in fish cells},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61774},
  year      = {1990},
  abstract  = {ln order to construct fish specific expression vectors for studies on gene regulation in vitro and in vivo a variety of heterologous enhancers and promoters from mammals and from viruses of higher vertebrate cells were tested for expression of the bacterial chloramphenicol acetyl transferase reporter gene in three teleost fish cell lines. Several viral enhancers were found to be constitutively active at high Ieveis. The human metallothionein promoter showed inducible expression in the presence of heavy metal Ions. A fish sequence was isolated that can be used as a homologous constitutively active promoter for expression of foreign genes. Using the human growth hormone gene with an active promoter in fish cells for transient expression insufficient splicing and Iack of translation were observed, pointing to limitations in the use of heterologous genes in gene transfer experiments. On the contrary, some heterologous promoters and enhancers functioned in fish c as weil as in their cell type of origin, indicating t at corresponding transcription factors are sufficient conserved between fish and human over a period of 900 million years of Independent evolution.},
  subject      = {Physiologische Chemie},
  language  = {en}
}
@article{ClaussWinklerLohmeyeretal.1990,
  author    = {Clauss, Gerd and Winkler, Christoph and Lohmeyer, J{\"u}rgen and Anders, Fritz and Schartl, Manfred},
  title     = {Oncofetal antigen in Xiphophorus detected by monoclonal antibodies directed against melanoma-associated antigens},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61784},
  year      = {1990},
  abstract  = {Monoclonal antlbodies (MAbs) directed against Xiphophorus melanoma cells were deve(oped and tested by lndirect immunofluorescence and Immunoperoxidase staining for reactivity with a panel of I 5 allogeneic tissues and 12 allogeneic cell llnes. The reactivity of such MAbs was restricted to melanoma cells from tumor biopsies and melanoma-derived cell lines. ln addition, all embryonie cells of all histiotypes from developmental stages later than mld·organogenesis and from corresponding short term in vitro cultures reacted with these MAbs. ln contrast, normal tissues and organs from adult fish dlsplayed no reactivity, thus implying that the melanoma-associated antigens detected by the MAbs described are oncofetal antigens.},
  subject      = {Physiologische Chemie},
  language  = {en}
}
@article{BarnekowJahnSchartl1990,
  author    = {Barnekow, Angelika and Jahn, Reinhard and Schartl, Manfred},
  title     = {Synaptophysin: a substrate for the protein tyrosine kinase pp60c-src in intact synaptic vesicles},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-86168},
  year      = {1990},
  abstract  = {Expression of pp60 c-src, the first well defined proto-oncogene product, is developmentally regulated and tissue-specific, with neuronal tissues displaying high amounts of the c-src encoded pp60 c-src kinase activity. In the central nervous system pp60 s-src is preferentially expressed in regions characterized by a high content of grey matter and elevated density of nerve terminals. In this study we show for the first time a direct interaction between pp60 c-src and synaptophysin as a physiological target protein in neurons by demonstrating that endogenous pp60 c-src is able to phosphorylate synaptophysin (p38). p38 is a major constituent of the synaptic vesicle membrane protein and is thought to play a key role in the exocytosis of small synaptic vesicles and possibly small clear vesicles in neuroendocrine cells.},
  subject      = {Synaptophysin},
  language  = {en}
}
@article{SchartlNandaSchluppetal.1990,
  author    = {Schartl, Manfred and Nanda, Indrajit and Schlupp, Ingo and Parzefall, Jakob and Schmid, Michael and Epplen, J{\"o}rg T.},
  title     = {Genetic variation in the clonal vertebrate Poecilia formosa is limited to few truly hypervariable loci},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-86359},
  year      = {1990},
  abstract  = {No abstract available.},
  subject      = {Amazon Molly},
  language  = {en}
}
@article{SchartlSchartl1990,
  author    = {Schartl, Angelika and Schartl, Manfred},
  title     = {Genes and cancer: Molecular biology of the melanoma oncogene of Xiphophorus},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-72670},
  year      = {1990},
  abstract  = {No abstract available.},
  subject      = {Schwertk{\"a}rpfling},
  language  = {en}
}
@article{SchartlSchluppSchartletal.1991,
  author    = {Schartl, Manfred and Schlupp, Ingo and Schartl, Angelika and Meyer, Manfred K. and Nanda, Indrajit and Schmid, Michael and Epplen, J{\"o}rg T. and Parzefall, Jakob},
  title     = {On the stability of dispensable constituents of the eukaryotic genome: Stability of coding sequences versus truly hypervariable sequences in a clonal vertebrate, the amazon molly, Poecilia formosa},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61731},
  year      = {1991},
  abstract  = {In dooal unisexual vertebrales, the genes specifying the males become dispensable. To study tbe rate of such geoes the gynogeoetic all-female fisb Poecilillfonnolll was treated with androgens. Phenotypic males were obtained that exbibited the complete set of male cbaracteristics of dosely related gooocboristic species, induding body proportions, pigmentation, the extremely complex insemination apparatus of poecil{\"u}d fish, sexual bebavior, and spermatogeoesls. Tbe apparent stabllity of such genic structures, induding those involved in androgen regulation, is contrasted by high instability of noncoding sequeaces. Frequent mutations, thelr donal transmission, and at least two truly hypervariable Iod leading to individual difl'ereaces between these othenrise donal organisms were detected by DNA fingerprinting. These observations substantiate the concept that also in "ameiotic" vertebrates certain compartments of the genome are more prooe to mutatiooal alterations than others.},
  subject      = {Physiologische Chemie},
  language  = {en}
}
@article{WinklerVielkindSchartl1991,
  author    = {Winkler, Christoph and Vielkind, J{\"u}rgen R. and Schartl, Manfred},
  title     = {Transient expression of foreign DNA during embryonic and larval development of the medaka fish (Oryzias latipes)},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61743},
  year      = {1991},
  abstract  = {Species of small fish are becoming useful tools for studies on vertebrate development. Wehave investigated the developing embryo of the Japanese medaka for its application as a transient expression system for the in vivo analysis of gene regulation and function. The temporaland spatial expression patterns ofbacterial chloramphenicol acetyltransferase and galactosidase reporter genes injected in supercoiled plasmid form into the cytoplasm of one cell of the two-cell stage embryo was promoter-specific. The transient expression was found to be mosaic within the tissue and organs reflecting the unequal distribution of extrachromosomal foreign DNA and the intensive cell mixing movements that occur in fish embryogenesis. The expression data are consistent with data on DNA fate. Foreign DNA persisted during embryogenesis and was still detectable in some 3- and 9-month-old adult fish; it was found in high molecular weight form as weil as in circular plasmid conformations. The DNA was replicated during early and late embryogenesis. Our data indicate that the developing medaka embryo is a powerful in vivo assay system for studies of gene regulation and function.},
  subject      = {Physiologische Chemie},
  language  = {en}
}
@article{SchluppParzefallSchartl1991,
  author    = {Schlupp, I. and Parzefall, J. and Schartl, Manfred},
  title     = {Male mate choice in mixed bisexual/-unisexual breeding complexes of Poecilia (Teleostei: Poeciliidae)},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-80309},
  year      = {1991},
  abstract  = {The livebearing all-female fish Poecilia formosa reproduces by gynogenesis, a modified form of parthenogenesis. P. formosa forms at least two breeding complexes: in its northern range it exists sympatrically with Poecilia latipinna and in its southern range with Poecilia mexicana. Differences between these complexes and their possible origin are discussed. Embryogenesis is triggered by sperm of males of these closely related sympatric species. Because inheritance is stricdy maternal, from the male point of view energy and time invested are totally lost. In this study we wanted to elucidate whether males are able to distinguish between conspecific and parasitic females. It could be shown that males are able to distinguish females optically, but that this ability was obscured as soon as chemical and/or tactile contact was possible. Furthermore, we found that females in an attractive phase of their sexual cycle are always preferred, regardless of species. This is possibly the mechanism by which parasitic females obtain the matings they need to reproduce.},
  subject      = {Poecilia (Teleostei: Poeciliidae)},
  language  = {en}
}
@article{MalitschekSchartl1991,
  author    = {Malitschek, B. and Schartl, Manfred},
  title     = {Rapid identification of recombinant baculoviruses using PCR},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-80328},
  year      = {1991},
  abstract  = {no abstract available},
  subject      = {PCR},
  language  = {en}
}
@article{SchartlErbeldingDenkNandaetal.1991,
  author    = {Schartl, Manfred and Erbelding-Denk, Claudia and Nanda, Indrajit and Schmid, Michael and Schr{\"o}der, Johannes Horst and Epplen, J{\"o}rg T.},
  title     = {Mating success of subordinate males in a poeciliid fish species, Limia perugiae},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-86349},
  year      = {1991},
  abstract  = {No abstract available.},
  subject      = {Lebendgeb{\"a}rende Zahnkarpfen},
  language  = {en}
}
@article{AdamMauelerSchartl1991,
  author    = {Adam, Dieter and Maueler, Winfried and Schartl, Manfred},
  title     = {Transcriptional activation of the melanoma inducing Xmrk oncogene in Xiphophorus},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-87584},
  year      = {1991},
  abstract  = {The melanoma inducing locus of Xiphophorus encodes a tumorigenic version of a novel putative receptor tyrosine kinase (Xmrk). To elucidate the mechanism of oncogenic activation of Xmrk, we compared the structure and expression of two oncogenic loci with the corresponding proto-oncogene. Only minor structural alterations were found to be specific for the oncogenic Xmrk genes. Marked overexpression of the oncogene transcripts in melanoma, which are approximately 1 kb shorter than the proto-oncogene transcript, correlates with the malignancy of the tumors. The tumor transcripts are derived from an alternative transcription start site that is used only in the oncogenic loci. Thus, oncogenic activation of the melanoma inducing Xmrk gene appears primarily to be due to novel transcriptional control and overexpression.},
  subject      = {Schwertk{\"a}rpfling},
  language  = {en}
}
@article{HannigOttilieSchartl1991,
  author    = {Hannig, Gerhard and Ottilie, Sabine and Schartl, Manfred},
  title     = {Conservation of structure and expression of the c-yes and fyn genes in lower vertebrates},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-86723},
  year      = {1991},
  abstract  = {The src-gene family in mammals and birds consists of 9 closely related protein tyrosine kinases. We have cloned the c-yes and fyn bomologues of the src-family from the teleost fish Xiphophorus helleri. Both genes show a high degree of sequence conservation and exhibit all structural motifs diagnostic for functional src-like protein tyrosine kinases. Sequence comparisons revealed three domains (exon 2, exons 3--6, exons 7-12) which evolve at different rates. Both genes exhibit an identical expression pattern, with preferential expression in neural tissues. No transcripts of c-yes were found in liver wbich is contrary to the situation in higher vertebrales. In malignant melanoma, elevated Ieveis of c-yes andfyn were detected indicating a possible function during secondary steps of tumor progression for src-related tyrosine kinases.},
  subject      = {Konservierung},
  language  = {en}
}
@incollection{EpplenAmmerEpplenetal.1991,
  author    = {Epplen, J. T. and Ammer, H. and Epplen, C. and Kammerbauer, C. and Mitreiter, R. and Roewer, L. and Schwaiger, W. and Steimle, V. and Zischler, H. and Albert, E. and Andreas, A. and Beyermann, B. and Meyer, W. and Buitkamp, J. and Nanda, I. and N{\"u}rnberg, P. and Pena, S. D. J. and P{\"o}che, H. and Sprecher, W. and Schartl, Manfred and Weising, K. and Yassouridis, A.},
  title     = {Oligonucleotide fingerprinting using simple repeat motifs: a convenient, ubiquitously applicable method to detect hypervariability for multiple purposes},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-86371},
  publisher      = {Universit{\"a}t W{\"u}rzburg},
  year      = {1991},
  abstract  = {A panel of simple repetitive oligonucleotide probes has been designed and tested for multilocus DNA fingerprinting in some 200 fungal, plant and animal species as well as man. To date at least one of the probes has been found to be informative in each species. The human genome, however, has been the major target of many fingerprintins studies. Using the probe (CAC)5 or (GTG)5, individualization of all humans is possible except for monozygotic twins. Paternity analyses are now perfonned on a routine basis by the use of multilocus fingerprints, inctuding also cases of deficiency, i.e. where one of the parents is not available for analysis. In forensie science stain analysis is feasible in all tissue remains containing nuc)eated cells. Depending on the degree of DNA degradation a variety of oligonucleotides are informative, and they have been proven useful in actual case work. Advantages in comparison to other methods including enzymatic DNA amplification techniques (PCR) are evident. Fingerprint patterns of tumors may be changed due to the gain or loss of chromosomes and/or intrachromosomal deletion and amplification events. Locus-specific probes were isolated from the human (CAC)5/( GTG)5 fingerprint with a varying degree of informativeness (monomorphic versus truly hypervariable markers). The feasibility of three different approaches. for the isolation of hypervariable mono-locus probes was evaluated. Finally, one particular mixed simple (gt)n(ga)m repeat locus in the second intron of the HLA-DRB genes has been scrutinized to allow comparison of the extent of exon-encoded (protein-) polymorphisms versus intronie bypervariability of simple repeats: adjacent to a single gene sequence (e.g. HLA-DRB1*0401) many different length alleles were found. Group-specific structures of basic repeats were identified within the evolutionarily related DRB alleles. As a further application it is suggested here that due to the ubiquitous interspersion of their targets, short probes for simple repeat sequences are especially useful tools for ordering genomic cosmid, yeast artificial chromosome and phage banks.},
  subject      = {DNS},
  language  = {en}
}
@incollection{AdamSchartlAndexingeretal.1991,
  author    = {Adam, D. and Schartl, A. and Andexinger, S. and H{\"o}lter, S. and Wilde, B. and Schartl, Manfred},
  title     = {Genetic factors in tumour formation: The melanoma-inducing gene of Xiphophorus},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-86388},
  publisher      = {Universit{\"a}t W{\"u}rzburg},
  year      = {1991},
  abstract  = {No abstract available.},
  subject      = {Humangenetik},
  language  = {en}
}
@article{SchartlAdam1992,
  author    = {Schartl, Manfred and Adam, Dieter},
  title     = {Molecular cloning, structural characterization, and analysis of transcription of the melanoma oncogene of xiphophorus},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61989},
  year      = {1992},
  abstract  = {No abstract available},
  subject      = {Physiologische Chemie},
  language  = {en}
}
@article{SchluppParzefallEpplenetal.1992,
  author    = {Schlupp, Ingo and Parzefall, Jakob and Epplen, J{\"o}rg T. and Nanda, Indrajit and Schmid, Michael and Schartl, Manfred},
  title     = {Pseudomale behaviour and spontaneous masculinization in the all-female teleost Poecilia formosa (Teleostei: Poeciliidae)},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61688},
  year      = {1992},
  abstract  = {Pseudosexual behaviour is a rare phenomenon associated with unisexuality in vertebrates. In the gynogenetic, all-female teleost Poecilia formosa, rare individuals occur that resemble males of closely related gonochoristic species both in behaviour and external morphology. These masculinized gynogens and normal gynogens are members of the same clone, as demonstrated by DNA-fingerprinting. The behaviour of these masculinized gynogens is described and compared to the behaviour of the gonochoristic species Poecilia mexicana, P. latipinna and their hybrid as weil as androgen-treated individuals of P. formosa. No statistically significant difTerences were found between masculinized gynogens and hormonetreated individuals nor between the gonochoristic P. mexicana and P. latipinna males. Differences exist between gonochoristic and unisexual species. Passihle causes and effects of masculinized gynogens are discussed.},
  subject      = {Physiologische Chemie},
  language  = {en}
}
@article{HongSchartl1992,
  author    = {Hong, Yunhan and Schartl, Manfred},
  title     = {Structure of the rainbow trout metallothionein A gene},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61679},
  year      = {1992},
  abstract  = {To investigate the regulation of metallothionein-encoding genes in fish, we have isolated and sequenced the rainbow trout metallothionein-A-encoding gene (tMT-A) by polymerase chain reaction. This gene spans about 1.1 kb, consists of three exons and two introns, and has an A+ T-rieb 5' -region which contains a TATAAA signal, and two metal responsive elements (MREs). The transcription start point is centered around an A residue 81 nt upstream of the ATG codon.},
  subject      = {Physiologische Chemie},
  language  = {en}
}
@article{WittbrodtLammersMalitscheketal.1992,
  author    = {Wittbrodt, Joachim and Lammers, Reiner and Malitschek, Barbara and Ullrich, Axel and Schartl, Manfred},
  title     = {Xmrk receptor tyrosine kinase is activated in Xiphophorus malignant melanoma},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61699},
  year      = {1992},
  abstract  = {Xmrk encodes a putative transmembrane glycoprotein of the tyrosine kinase family and is a melanoma-inducing gene in Xiphophorus. We attempted to investigate the biological function of the putative Xmrk receptor by characterizing its signalling properties. Since a potential Iigand for Xmrk has not yet been identified, it has been difficult to analyse the biochemical properlies and biological function of this cell surface protein. In an approach towards such analyses, the Xmrk extracellular domain was replaced by the closely related Iigand-binding domain sequences of the human epidennal growth factor receptor (HER) and the ligand-induced activity of the chimeric HER-Xmrk proteinwas examined. We show that the Xmrk protein is a functional receptor tyrosine kinase, is highly active in malignant melanoma and displays a constitutive autophosphorylation activity possibly due to an activating mutation in its extracellular or transmembrane domain. In the focus formation assay the HER-Xmrk chimera is a potent transfonning protein equivalent to other tyrosine kinase oncoproteins.},
  subject      = {Physiologische Chemie},
  language  = {en}
}
@article{NandaSchartlFeichtingeretal.1992,
  author    = {Nanda, Indrajit and Schartl, Manfred and Feichtinger, Wolfgang and Epplen, J{\"o}rg T. and Schmid, Michael},
  title     = {Early stages of sex chromosome differentiation in fish as analysed by simple repetitive DNA sequences},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61715},
  year      = {1992},
  abstract  = {Animal sex chromosome evolution has started on different occasions with a homologous pair of autosomes leading to morphologically differentiated gonosomes. In contrast to other vertebrate classes, among fishes cytologically dernonstrahle sex chromosomes are rare. In reptiles, certain motifs of simple tandemly repeated DNA sequences like (gata)\(_n\)/(gaca)\(_m\) are associated with the constitutive heterochromatin of sex chromosomes. In this study a panel of simple repetitive sequence probes was hybridized to restriction enzyme digested genomic DNA of poeciliid fishes. Apparent male heterogamety previously established by genetic experiments in Poecilia reticulata (guppy) was correlated with male-specific hybridization using the (GACA)\(_4\) probe. The (GATA)\(_4\) oligonucleotide identifies certain male guppies by a Y chromosomal polymorphism in the outbred population. In cantrast none of the genetically defined heterogametic situations in Xiphophorus could be verified consistently using the collection of simple repetitive sequence probes. Only individuals from particular populations produced sex-specific patterns of hybridization with (GATA)\(_4\). Additional poeciliid species (P. sphenops, P. velifera) harbour different sex-specifically organized simple repeat motifs. The observed sex-specific hybridization patterns were substantiated by banding analyses of the karyotypes and by in situ hybridization using the (GACA)\(_4\) probe.},
  subject      = {Physiologische Chemie},
  language  = {en}
}
@article{OttilieRaulfBarnekowetal.1992,
  author    = {Ottilie, S. and Raulf, F. and Barnekow, A. and Hannig, G. and Schartl, Manfred},
  title     = {Multiple src-related kinase genes, srk1-4, in the fresh water sponge Spongilla lacustris},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-80282},
  year      = {1992},
  abstract  = {In one of the simplest metazoan organisms, the sponge Spongilla lacustris, at least four different src-related kin ase genes (srkl-4) are expressed, aD of which show a high degree of similarity to the c-src genes of vertebrates. Whereas srk2 and srk3 are c1early unrelated at the nucleic acid level, srkl and srk4 share identical sequences in the 5' parts of their cDNAs. The cloning of several primer extension clones and genomic polymerase chain re action experiments confirmed the hypo thesis of an alternative splicing of tandemly arranged carboxyterminal parts of srkl and srk4. The genomic sequence encoding both proteins was found to be interrupted at the splice point by an intron which is located in the same position as one of the introns in the chicken src gene, which is the only gene conserved in invertebrates and vertebrates. All four srk genes are expressed in adult sponges as mRNA transcripts of about 2.2 kb. Tyrosine kin ase activity of a src-related kin ase could be detected in adult sponges but not in their resting form (gemmulae), and may reflect the activity of the srk protein products. Spongilla lacustris is the simplest organism from which a pro tein tyrosine kinase gene has been isolated. The presence of at least four such genes in the evolutionary ancient and primitive phylum Porifera suggests that tyrosine kinase genes arose concomitantly with or shortly after the appearance of multicellular organisms and that their activity may be involved in aggregation and cell-cell recognition.},
  subject      = {Spongilla lacustris},
  language  = {en}
}
@article{WinklerHongWittbrodtetal.1992,
  author    = {Winkler, Christoph and Hong, Yunhan and Wittbrodt, Joachim and Schartl, Manfred},
  title     = {Analysis of heterologous and homologous promoters and enhancers in vitro and in vivo by gene transfer into Japanese medaka (Oryzias latipes) and Xiphophorus},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-86796},
  year      = {1992},
  abstract  = {Efficient expression systems are required for analysis of gene regulation and function in teleost fish. To develop such systems, a nurober of inducible or constitutive promoter and enhancer sequences of fish or higher vertebrate origin were tested for activity in a variety of fish celllines andin embryos of the Japanese medaka fish (Oryzias latipes) and Xiphophorus. The activity of the different promoterenhancer combinations were quantitated. Considerable differences were found for some constructs if tested in vitro or in vivo. From the data obtained, a set of expression vectors for basic research as weH as for aquaculture purposes were established.},
  subject      = {Schwertk{\"a}rpfling},
  language  = {en}
}
@article{HongSchartl1993,
  author    = {Hong, Yunhan and Schartl, Manfred},
  title     = {Sequence of the growth hormone (GH) gene from the silver carp (Hypophthalmichthys molitrix) and evolution of GH genes in vertebrates},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61620},
  year      = {1993},
  abstract  = {The silver carp (Hypophthalmichthys molitrix) growth hormone (GH) genewas isolated and sequenced following amplification from genomic DNA by the polymerase chain reaction. The gene spans a region of approx. 2.5 kb nucleotides (nt) and consists of five exons. The sequence predicts a polypeptide of 210 amino acids (aa) including a putative signal peptide of 22 hydrophobic aa residues. The arrangement of exons and introns is identical to the GH genes of common carp, grass carp, and very similar to mammals and birds, but quite different from that for the GH genes of tilapia and salmonids. The silver carp GH gene shares a high homology at the nt and aa Ievels with those of grass carp (95.3\% nt, 99.5\% aa) and of common carp (81\% nt, 95.7\% aa).},
  subject      = {Physiologische Chemie},
  language  = {en}
}
@article{AdamDimitrijevicSchartl1993,
  author    = {Adam, Dieter and Dimitrijevic, Nicola and Schartl, Manfred},
  title     = {Tumor suppression in Xiphophorus by an accidentally acquired promoter},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61630},
  year      = {1993},
  abstract  = {Melanoma formation in the teleost Xiphophorus is caused by a dominant genetic locus, Tu. This locus includes the Xmrk oncogene, which encodes a receptor tyrosine kinase. Tumor induction is. suppressed in wild-type fish by a tumor suppressor locus, R. Molecular genetic analyses revealed that the Tu locus emerged by nonhomologaus recombination of the Xmrk proto-oncogene with a previously uncharacterized sequence, D. This event generated an additional copy of Xmrk with a new promoter. Suppression of the new Xmrk promoter by R in parental fish and its deregulation in hybrids explain the genetics of melanoma formation in Xiphophorus.},
  subject      = {Physiologische Chemie},
  language  = {en}
}
@article{SchartlErbeldingDenkHolteretal.1993,
  author    = {Schartl, Manfred and Erbelding-Denk, Claudia and Holter, Sabine and Nanda, Indrajit and Schmid, Michael and Schroder, Johannes H. and Epplen, J{\"o}rg T.},
  title     = {Reproductive failure of dominant males in the poeciliid fish Limia perugiae determined by DNA fingerprinting},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61643},
  year      = {1993},
  abstract  = {Hierarchical structures among male indlviduals in a population are frequently reflected ln differences in aggressive and reproductive behavior and access to the females. In general, sodal dominance requires the Investments, which in turn then may have to be compensated for by high reproductive success. However, this hypothesls has so far only been sufficiently tested in small mating groups (one or two males with one or two females) due to the difficulties of determining paternity by conventional methods. DNA fingerprinting overcomes these problems by offering the possibility to determine genetic relationships and mating patterns within larger groups [Borke, T. (1989) Trends Ecol. Evol. 4, 139-144]. We show here that in the poecUiid fish Limia perugitu, in small matlng groups the dominant male has 8 mating success of 100\%, whereas ln larger groups lts contribution to the offspring unexpectedly drops to zero.},
  subject      = {Physiologische Chemie},
  language  = {en}
}
@article{NandaSchartlEpplenetal.1993,
  author    = {Nanda, Indrajit and Schartl, Manfred and Epplen, J{\"o}rg T. and Feichtinger, Wolfgang and Schmid, Michael},
  title     = {Primitive sex chromosomes in poeciliid fishes harbor simple repetitive DNA sequences},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61659},
  year      = {1993},
  abstract  = {The demonstration ofthe chromosomal mode ofsex determinationvia genetic experiments as well as the absence of heteromorphic sex chromosomes affirm poeciliid fishes as a unique group among vertebrates that are endowed with the mostprimitive form of sex chromosornes. In many different taxa the evolutionary process involved in the differentiation ofadvanced sex chromosomes is outlined through sex specifically organized repetitive sequences. In this investigation hydridization of synthetic probes specific to genomic simple repeat motifs uncovers a sex-specific hybridization pattern in certain viviparaus fishes ofthe family Poeciliidae. The hybridization pattern together with specific staining ofthe constitutive heterochromatin by C-banding reveals heterogamety in males (Poecilia reticulata) as weil as in females (P. sphenops). In P. velifera, however, C-banding alone fails to unravel the heterogametic status. The female specific W-chromosome can be detected by simple repetitive sequence probes. Therefore, the principal significance of heterochromatization as a means of generating differentiated sex chromosomes is evident.},
  subject      = {Physiologische Chemie},
  language  = {en}
}
@article{HongWinklerBremetal.1993,
  author    = {Hong, Yunhan and Winkler, Christoph and Brem, Gottfried and Schartl, Manfred},
  title     = {Development of a heavy metal-inducible fish-specific expression vector for gene transfer in vitro and in vivo},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61666},
  year      = {1993},
  abstract  = {The promoter of the rainbow trout metallothionein B gene ( tMTb) was isolated from genomic DNA by the polymerase chain reaction (PCR ), fused to the bacterial chloramphenicol acetyltransferase (CAT) genein an expression vector, and functionally analyzed in one human cellline and four fish celllines. This promoter exhibited an extremely low basal expression in all celllines and was zincand cadmium-inducible except in the fish melanoma cell line where the promoter was completely inactive. The metal-induced expression patterns were cellline-specific. In general the fish promoter was more species- and cell type-specific than its human counterpart. In a transient assay it was functional in developing embryos of the medaka ( Oryzias /atipes). These properties make this promoter suitable for inducible, tissue-specific expression of transgenes and for in vivo studies of gene function and regulation.},
  subject      = {Physiologische Chemie},
  language  = {en}
}
@article{MaeuelerSchartlSchartl1993,
  author    = {M{\"a}ueler, Winfried and Schartl, Angelika and Schartl, Manfred},
  title     = {Different expression patterns of oncogenes and proto-oncogenes in hereditary and carcinogen-induced tumors of Xiphophorus},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61592},
  year      = {1993},
  abstract  = {Hereditary melanoma in Xiphophorus hybrids canying the melanoma·induclng Tu-Sd locus is caused by transcriptional activation of the Xmrk gene that resides at the Tu·Sd locus and encodes a novel member of receptor tyrosine kinases (RTK). ln this study, a total of 17 hereditary melanomas from various hybrid genotypes harbouring 7 different Tu alleles were also found to aver-express the correspondlng Xmrlc alleles. The Ievei of over-expression correlated with the degree of malignancy of the melanoma. ln addition, Xsrc expression was high ln many malignant melanomas. Expression pattems and Ieveis of the Xiphophorus EGF-receptor gene (Xerb B), the c-myc (Xmyc), and the PDGF (Xsls) gene(s) were not intriguing. Transcription of the ras gene(s) may be correlated to secondary events of melanoma progression. Expression pattems of Xfms, the Xiphophorus CSF-1 receptor homologue, can be explained by different contents of infiltrating macrophages in the tumors. ln carcinogen-induced tumors includlng one melanoma no significant expression of the Xmrk oncogene could be detected. Xsrc expression, however, was strikingly high. This indicates that activation of oncogenes other than Xmrk ls instrumental in tumorigenesls of neoplasia of non-hereditary origin.},
  subject      = {Physiologische Chemie},
  language  = {en}
}
@article{SchliewenFrickeSchartletal.1993,
  author    = {Schliewen, U. and Fricke, H. and Schartl, Manfred and Epplen, J{\"o}rg T. and Paabo, S.},
  title     = {Which home for coelacanth?},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61606},
  year      = {1993},
  abstract  = {No abstract available},
  subject      = {Physiologische Chemie},
  language  = {en}
}
@article{CavariHongFunkensteinetal.1993,
  author    = {Cavari, Benzion and Hong, Yunhan and Funkenstein, Bruria and Moav, Boaz and Schartl, Manfred},
  title     = {All-fish gene constructs for growth hormone gene transfer in fish},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61612},
  year      = {1993},
  abstract  = {In order to develop all-fish expression vectors for microinjection into fertilized fish eggs, we have prepared the following cunstructs: rainbow trout metallothionein a/b and the gilthead seabream growth hormone cDNA (ptMTa-gbsGHcDNA, ptMTb-gsbGHcDNA), carp ß-actin gilthead seabream GH cDNA (pcAßgsbGHcDNA). The inducible metallothionein promoters a and b were cloned from rainbow trout, and the constitutive promoter ß-actin was isolated from carp. The metallothionein promoters were cloned by using the PCR technique. The tMTa contains 430 bp, while the tMTb contains 260 bp (Hong et al. 1992). These two promoters were introduced to pGEM-3Z containing the GH cDNA of Sparus aurata to form ptMTa-gsbGH and ptMTb-gsbGH, respectively. The carp cytoplasmic ß-actin gene was chosen as a source for isolating strong constitutive regulatory sequences. One of these regulatory sequences in pUC118 was Iigated to GH cDNA of S. aurata to form the pcAß-gsbGHcDNA. Expression of the constructs containing the metallothionein promoters was tested in fish cell culture and was found tobe induced effectively by zinc. The ptMTa gsb-GH cDNA construct was microinjected into fertilized carp eggs, and integration in the genome of carp was detected in the DNA isolated from fins at the age of two months.},
  subject      = {Physiologische Chemie},
  language  = {en}
}
@article{CavariFunkensteinChenetal.1993,
  author    = {Cavari, Benzion and Funkenstein, Bruria and Chen, Thomas T. and Gonzalez-Villasenor, Lucia Irene and Schartl, Manfred},
  title     = {Effect of growth hormone on the growth rate of the gilthead seabream (Sparus aurata), and use of different constructs for the production of transgenic fish},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-69765},
  year      = {1993},
  abstract  = {When bovine or human growth hormones (GH) were injected into 6 months old (about 10 g) gilthead seabream, the growth rate of the fish, as measured by changes in their weight, increased by only about 15\% compared with the saline-injected control. No effect or even slight inhibition of the growth rate was obtained when chicken or porcine GHs were injected. In a preliminary experiment, it was found that injection ofthe native GH increased the growth rate ofthe fish by about 20\% after treatment for only 2 weeks. An expression vector, using the pRE1 plasmid and transformation into MZl cells, produced the gilthead seabream GH, providing a supply for further experiments on the effect of the homologaus GH on growth. Two reporter genes, ß-galactosidase (lacZ) and melanoma oncogene of Xiphophorus (mrk YY), were microinjected into fertilized eggs of S. aurata. Expression of these two genes could be demonstrated in 2-day-old embryos, the lacZ gene by staining of its enzymatic product, and the mrk YY gene by its phenotypic expression.},
  subject      = {Goldbrasse},
  language  = {en}
}
@incollection{SchartlErbeldingDenkHoelteretal.1993,
  author    = {Schartl, Manfred and Erbelding-Denk, C. and H{\"o}lter, S. and Nanda, I. and Schmid, M. and Schr{\"o}der, J. H. and Epplen, J. T.},
  title     = {High mating success of low rank males in Limia perugiae (Pisces: Poeciliidae) as determined by DNA-fingerprinting},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-87132},
  publisher      = {Universit{\"a}t W{\"u}rzburg},
  year      = {1993},
  abstract  = {Hierarchical structures among male individuals in a population are frequently reflected in differences in aggressive and reproductive behaviour and access to the females. In general social dominance requires large investments which in turn may have to be compensated for by high reproductive success. However, this hypothesis has so far only been sufficiently tested in small mating groups due to the difficulties of determining paternity by classical methods using non-molecular markers. DNA fingerprinting overcomes these problems offering the possibility to determine genetic relationships and mating patterns within larger groups. Using this approach we have recently shown (Schartl et al., 1993) that in the poeciliid fish Limia perugiae in small mating groups the dominant male has 100\% mating success, while in larger groups its contribution to the offspring unexpectedly drops to zero. The reproductive failure under such social conditions is explained by the inability of the ex-male to protect all the females simultaneously against mating attempts of his numerous subordinate competitors.},
  subject      = {DNS},
  language  = {en}
}
@article{SchartlWittbrodtMaeueleretal.1993,
  author    = {Schartl, Manfred and Wittbrodt, J. and M{\"a}ueler, W. and Raulf, F. and Adam, D. and Hannig, G. and Telling, A. and Storch, F. and Andexinger, S. and Robertson, S. M.},
  title     = {Oncogenes and melanoma formation in Xiphoporus (Teleostei: Poeciliidae)},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-87149},
  year      = {1993},
  abstract  = {In Xiphophorus melanoma formation has been attributed by classical genetic findings to the overexpression of a cellular oncogene (Tu) due to elimination of the corresponding regulatory gene locus in hybrids. We have attempted to elucidate this phenomenon on the molecular biological level. Studies on the structure and expression of known proto-oncogenes revealed that several of these genes, especially the c-src gene of Xiphophorus, may act as effectors in establishing the neoplastic phenotype of the melanoma cells . However, these genes appear more to participate in secondary steps of tumorigenesis. Another gene, being termed Xmrk, which represents obviously a so far unknown proto-oncogene but with a cons iderably high similarity to the epidermal growth-factorreceptor gene, was mapped to the Tu-containing region of the chromosome. This gene shows features with respect to its structure and expression that seem to justify it to be regarded as a candidate for a gene involved in the primary processes leading to neoplastic transformation of pigment cells in Xiphophorus.},
  subject      = {Schwertk{\"a}rpfling},
  language  = {en}
}
@article{SchartlDimitrijevicSchartl1994,
  author    = {Schartl, A. and Dimitrijevic, N. and Schartl, Manfred},
  title     = {Evolutionary origin and molecular biology of the melanoma-inducing oncogene of Xiphophorus},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61954},
  year      = {1994},
  abstract  = {No abstract available},
  subject      = {Physiologische Chemie},
  language  = {en}
}
@inproceedings{GotzSchartl1994,
  author    = {Gotz, R. and Schartl, Manfred},
  title     = {The conservation of neurotrophic factors during vertebrate evolution},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61964},
  year      = {1994},
  abstract  = {No abstract available},
  subject      = {Physiologische Chemie},
  language  = {en}
}
@article{LubjuhnSchartlEpplen1994,
  author    = {Lubjuhn, T. and Schartl, Manfred and Epplen, J. T.},
  title     = {Methodik und Anwendungsgebiete des genetischen Fingerabdruckverfahrens},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61978},
  year      = {1994},
  abstract  = {No abstract available},
  subject      = {Physiologische Chemie},
  language  = {en}
}
@article{ErbeldingDenkSchroderSchartletal.1994,
  author    = {Erbelding-Denk, Claudia and Schroder, Johannes H. and Schartl, Manfred and Nanda, Indrajit and Schmid, Michael and Epplen, J{\"o}rg T.},
  title     = {Male polymorphism in Limia perugiae (Pisces: Poeciliidae)},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61573},
  year      = {1994},
  abstract  = {The male-polymorphic poeciliid fish, Limia perugiae, a small teleostean endemic to the southeast of the Caribbean island Hispafiola, consists of three male size morphs with uniform females. Large males differentiate at a size va:rying between 25 and 38 mm; intermediate males, between 21 and 25 mm. Under competition, !arge males exhibit an elaborate courtship display, whereas small males show only a sneak-chase behavior. Intermediate males adapt their tactics to the respective competitors. However, all malemorphs can switch from courtship display to sneak-chase behavior. In large mating groups with four males of different size and five or six virgin females, large dominant a-males as weil as small subordinate \(\delta\)-males did not produce any offspring. Unexpectedly, all progeny were sired exclusively by the intemediate subordinate ß- and \(\gamma\)-males. Breeding experiments with the three male morphs can best be explained by a model of Y -linked genes for small and !arge size which are both suspended by the activity of an autosomal recessive repressor responsible for the development of intermediate males. The dominant allele of the recessive repressor, in either its homoorits heterozygous state, activates the Y-chromosomal genes for !arge or small size, respectively. Accordingly, intermediate males may produce male offspring of all size classes, depending on the presence of either the Y-linked gene or the autosomal repressor.},
  subject      = {Physiologische Chemie},
  language  = {en}
}
@article{NakayamaForestiTewarietal.1994,
  author    = {Nakayama, Ichiro and Foresti, Fausto and Tewari, Rita and Schartl, Manfred and Chourrout, Daniel},
  title     = {Sex chromosome polymorphism and heterogametic males revealed by two cloned DNA probes in the ZW/ZZ fish Leporinus elongatus},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61583},
  year      = {1994},
  abstract  = {In order to study the divergence of teleost sex chromosomes, subtractive cloning was carried out between genomic DNA ofmales and females ofthe rainbow trout (XX/XY) and of Leporinus elongatus (ZW /ZZ). Inserts cloned in a plasmid vector were individually tested on Southern blots of DNA of males and females for sex specificity. No sex-specific insert was obtained from trout, but two out of ten inserts cloned from L. elongatus showed sex-specific patterns in this species: one corresponds to a sequence present on both Z and W chromosomes, while the other is W specific. Sequences of these two inserts show neither clear homology with other known sequences, nor an open reading frame. They cross-hybridize with the genomic DNA of Leporinusfriderici, but without sex-specific patterns. Twenty-four L. elongatus adults were sexed by gonadal observation, chromosomed examination and Southern hybridization with one or the other insert. Ten males and 11 females had chromosomes and hybridization patterns typical of their sex. One ZW female was recognized as a male with the W-specific probe. This was also the case for two unusual ZW males, one having a male hybridization pattern with the other probe. These three atypical individuals may result from single genetic exchanges between four regions of the Z and the W, giving rise to three atypical W chromosomes. Finding males with such atypical heterochromosomes in a female heterogametic species may indicate that a gradual transition occurs between the heterogametic systems.},
  subject      = {Physiologische Chemie},
  language  = {en}
}
@article{GoetzKoesterWinkleretal.1994,
  author    = {G{\"o}tz, Rudolf and K{\"o}ster, Reinhard and Winkler, Christoph and Raulf, Friedrich and Lottspeich, Friedrich and Schartl, Manfred and Thoenen, Hans},
  title     = {Neurotrophin-6 is a new member of the nerve growth factor family},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61544},
  year      = {1994},
  abstract  = {DURING vertebrale development, many neurons depend for survival and differentiation on their target cells\(^{1-3}\). The best documented mediator of such a retrograde trophic action is the neurotrophin nerve growth factor (NGF)\(^1\). NGF and the other known members of tbe neurotrophin family, brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT -3) and neurotrophin-4/5 (NT -4/5) are conserved as distinct genes over large evolutionary distances\(^{4 -6}\). Here we report the cloning of neurotrophin-6 (NT -6), a new member of this family from the teleost fish Xiphophorus. NT -6 distinguishes itself from the other known neurotrophins in that it is not found as a soluble protein in the medium of producing cells. The addition of heparin (but not chondroitin) effects the release of NT -6 from cell surface and extracellular matrix molecules. Recombinant purified NT -6 has a spectrum of actions similar to NGF on chick sympathetic and sensory neurons, albeit with a lower potency. NT -6 is expressed in tbe embryonie valvulla cerebelli; expression persists in some adult tissues. The interaction of NT-6 with heparin-binding molecuJes may modulate its action in the nervous system .},
  subject      = {Physiologische Chemie},
  language  = {en}
}
@article{MalitschekWittbrodtFischeretal.1994,
  author    = {Malitschek, Barbara and Wittbrodt, Joachim and Fischer, Petra and Lammers, Reiner and Ullrich, Axel and Schartl, Manfred},
  title     = {Autocrine stimulation of the Xmrk receptor tyrosine kinase in Xiphophorus melanoma cells and identification of a source for the physiological ligand},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61551},
  year      = {1994},
  abstract  = {The melanoma·inducing gene of Xiphophorus fish encodes the Xmrk receptor tyrosine kinase. U sing a highly specific antiserum p~oduced against the recombinant receptor expressed with a baculovirus, it is shown that Xmrk is the most abundant phosphotyrosine protein in fish melanoma and thus highly activated in the tumors. Studies on a melanoma cellline revealed that these cells produce an activity that considerably stimulates receptor autophosphorylation. The stimulating activity induces receptor down-regulation and can be depleted from the melanoma cellsupernatant by the immobilized recombinant receptor protein. The fish melanoma cells can thus be considered autocrine tumor cells providing a source for future purification and characterization of the Xmrk ligand.},
  subject      = {Physiologische Chemie},
  language  = {en}
}
@article{MeyerMorrisseySchartl1994,
  author    = {Meyer, Axel and Morrissey, Jean M. and Schartl, Manfred},
  title     = {Recurrent origin of a sexually selected trait in Xiphophorus fishes inferred from a molecular phylogeny},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61569},
  year      = {1994},
  abstract  = {DARWIN\(^1\) believed that sexual selection accounts for the evolution of exaggerated male ornaments, such as the sword-like caudal fin extensions of male fishes of the genus Xiphophorus, that appear detrimental to survival. Swordtails continue to feature prominently in empirical work and theories of sexual selection; the pre-existing bias hypothesis has been offered as an explanation for the evolution of swords in these fishes\(^{2,3}\). Based upon a largely morphological phylogeny, this hypothesis suggests that female preference to mate with sworded males arose in ancestrally swordless species, thus pre-dating the origin of the sword itself and directly driving its evolution. Here we present a molecular phylogeny (based on mitochondrial and nuclear DNA sequences) of Xiphophorus which differs from the traditional one: it indicates that the sword originated and was lost repeatedly. Our phylogeny suggests that the ancestor of the genus is more likely to have possessed a sword than not, thus questioning the applicability of the pre-existing bias hypothesis as an explanation for the cvolution of this sexually selected trait.},
  subject      = {Physiologische Chemie},
  language  = {en}
}
@inproceedings{SchreibmanSchartlKallmanetal.1994,
  author    = {Schreibman, Martin P. and Schartl, Manfred and Kallman, Klaus D. and Magliulo-Cepriano, Lucia},
  title     = {Molecular approaches to study the genetic regulation of the fish reproductive system},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-86679},
  year      = {1994},
  abstract  = {No abstract available.},
  subject      = {Fische},
  language  = {en}
}
@incollection{AltschmiedSchartl1994,
  author    = {Altschmied, Joachim and Schartl, Manfred},
  title     = {Genetics and molecular biology of tumour formation in Xiphophorus},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-69752},
  publisher      = {Universit{\"a}t W{\"u}rzburg},
  year      = {1994},
  abstract  = {No abstract available.},
  subject      = {Schwertk{\"a}rpfling},
  language  = {en}
}
@article{WinklerWittbrodtLammersetal.1994,
  author    = {Winkler, Christoph and Wittbrodt, Joachim and Lammers, Reiner and Ullrich, Axel and Schartl, Manfred},
  title     = {Ligand-dependent tumor induction in medakafish embryos by a Xmrk receptor tyrosine kinase transgene},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-87107},
  year      = {1994},
  abstract  = {Xmrk encodes a subclass 1 receptor tyrosine kinase (RTK) which has been cloned from the melanomainducing locus Tu of the poeciliid fish Xiphophorus. To demonstrate a high oncogenic potential in vivo we transferred the gene into early embryos of the closely related medakafish. Ectopic expression of the Xmrk oncogene under the control of a strong, constitutive promoter (CMVTk) led to the induction of embryonic tumors with high incidence, after short latency periods, and with a specific pattern of affected tissues. We demonstrate ligand-dependent transformation in vivo using a chimeric receptor consisting of the extracellular and transmembrane domains of the human EGF receptor (HER) and the cytoplasmatic domain of Xmrk. Expression of the chimeric receptor alone does not lead to ldnase activation or induction of tumors. Coexpression of the chimera with its corresponding ligand, human transforming growth factor alpha (bTGF(X), however, results in the activation of the chimeric RTK. In injected fish embryos the induction of the neoplastic growth is observed with similar incidence and tissue distribution as in embryos carrying the native Xmrk oncogene suggesting that the ligand as well as factors downstream of tbe RTK are required for tumor formation. In this study we show single-step induction of tumors by ectopic expression of RTKs in vivo substantiating tbe significance of autocrine stimulation in RTK induced tumors in vertebrales.},
  subject      = {Japank{\"a}rpfling},
  language  = {en}
}
@article{MeierjohannHufnagelWendeetal.2010,
  author    = {Meierjohann, Svenja and Hufnagel, Anita and Wende, Elisabeth and Kleinschmidt, Markus A. and Wolf, Katarina and Friedl, Peter and Gaubatz, Stefan and Schartl, Manfred},
  title     = {MMP13 mediates cell cycle progression in melanocytes and melanoma cells: in vitro studies of migration and proliferation},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68335},
  year      = {2010},
  abstract  = {Background: Melanoma cells are usually characterized by a strong proliferative potential and efficient invasive migration. Among the multiple molecular changes that are recorded during progression of this disease, aberrant activation of receptor tyrosine kinases (RTK) is often observed. Activation of matrix metalloproteases goes along with RTK activation and usually enhances RTK-driven migration. The purpose of this study was to examine RTKdriven three-dimensional migration of melanocytes and the pro-tumorigenic role of matrix metalloproteases for melanocytes and melanoma cells. Results: Using experimental melanocyte dedifferentiation as a model for early melanomagenesis we show that an activated EGF receptor variant potentiates migration through three-dimensional fibrillar collagen. EGFR stimulation also resulted in a strong induction of matrix metalloproteases in a MAPK-dependent manner. However, neither MAPK nor MMP activity were required for migration, as the cells migrated in an entirely amoeboid mode. Instead, MMPs fulfilled a function in cell cycle regulation, as their inhibition resulted in strong growth inhibition of melanocytes. The same effect was observed in the human melanoma cell line A375 after stimulation with FCS. Using sh- and siRNA techniques, we could show that MMP13 is the protease responsible for this effect. Along with decreased proliferation, knockdown of MMP13 strongly enhanced pigmentation of melanocytes. Conclusions: Our data show for the first time that growth stimuli are mediated via MMP13 in melanocytes and melanoma, suggesting an autocrine MMP13-driven loop. Given that MMP13-specific inhibitors are already developed, these results support the evaluation of these inhibitors in the treatment of melanoma.},
  subject      = {Medizin},
  language  = {en}
}
@article{TeutschbeinHaydnSamansetal.2010,
  author    = {Teutschbein, Janka and Haydn, Johannes M. and Samans, Birgit and Krause, Michael and Eilers, Martin and Schartl, Manfred and Meierjohann, Svenja},
  title     = {Gene expression analysis after receptor tyrosine kinase activation reveals new potential melanoma proteins},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-67900},
  year      = {2010},
  abstract  = {Background: Melanoma is an aggressive tumor with increasing incidence. To develop accurate prognostic markers and targeted therapies, changes leading to malignant transformation of melanocytes need to be understood. In the Xiphophorus melanoma model system, a mutated version of the EGF receptor Xmrk (Xiphophorus melanoma receptor kinase) triggers melanomagenesis. Cellular events downstream of Xmrk, such as the activation of Akt, Ras, B-Raf or Stat5, were also shown to play a role in human melanomagenesis. This makes the elucidation of Xmrk downstream targets a useful method for identifying processes involved in melanoma formation. Methods: Here, we analyzed Xmrk-induced gene expression using a microarray approach. Several highly expressed genes were confirmed by realtime PCR, and pathways responsible for their induction were revealed using small molecule inhibitors. The expression of these genes was also monitored in human melanoma cell lines, and the target gene FOSL1 was knocked down by siRNA. Proliferation and migration of siRNA-treated melanoma cell lines were then investigated. Results: Genes with the strongest upregulation after receptor activation were FOS-like antigen 1 (Fosl1), early growth response 1 (Egr1), osteopontin (Opn), insulin-like growth factor binding protein 3 (Igfbp3), dual-specificity phosphatase 4 (Dusp4), and tumor-associated antigen L6 (Taal6). Interestingly, most genes were blocked in presence of a SRC kinase inhibitor. Importantly, we found that FOSL1, OPN, IGFBP3, DUSP4, and TAAL6 also exhibited increased expression levels in human melanoma cell lines compared to human melanocytes. Knockdown of FOSL1 in human melanoma cell lines reduced their proliferation and migration. Conclusion: Altogether, the data show that the receptor tyrosine kinase Xmrk is a useful tool in the identification of target genes that are commonly expressed in Xmrk-transgenic melanocytes and melanoma cell lines. The identified molecules constitute new possible molecular players in melanoma development. Specifically, a role of FOSL1 in melanomagenic processes is demonstrated. These data are the basis for future detailed analyses of the investigated target genes.},
  language  = {en}
}
@article{LaisneyBraaschWalteretal.2010,
  author    = {Laisney, Juliette A. G. C. and Braasch, Ingo and Walter, Ronald B. and Meierjohann, Svenja and Schartl, Manfred},
  title     = {Lineage-specific co-evolution of the Egf receptor/ligand signaling system},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-67922},
  year      = {2010},
  abstract  = {Background: The epidermal growth factor receptor (Egfr) with its numerous ligands has fundamental roles in development, cell differentiation and physiology. Dysfunction of the receptor-ligand system contributes to many human malignancies. Consistent with such various tasks, the Egfr gene family has expanded during vertebrate evolution as a consequence of several rounds of whole genome duplication. Of particular interest is the effect of the fish-specific whole genome duplication (FSGD) on the ligand-receptor system, as it has supplied this largest group of vertebrates with additional opportunities for sub- and/or neofunctionalization in this signaling system. Results: We identified the predicted components of the Egf receptor-ligand signaling system in teleost fishes (medaka, platyfish, stickleback, pufferfishes and zebrafish). We found two duplicated egfr genes, egfra and egfrb, in all available teleost genomes. Surprisingly only one copy for each of the seven Egfr ligands could be identified in most fishes, with zebrafish hbegf being the only exception. Special focus was put on medaka, for which we more closely investigated all Egf receptors and Egfr ligands. The different expression patterns of egfra, egfrb and their ligands in medaka tissues and embryo stages suggest differences in role and function. Preferential co-expression of different subsets of Egfr ligands corroborates the possible subfunctionalization and specialization of the two receptors in adult tissues. Bioinformatic analyses of the ligand-receptor interface between Egfr and its ligands show a very weak evolutionary conservation within this region. Using in vitro analyses of medaka Egfra, we could show that this receptor is only activated by medaka ligands, but not by human EGF. Altogether, our data suggest a lineage-specific Egfr/Egfr ligand co-evolution. Conclusions: Our data indicate that medaka Egfr signaling occurs via its two copies, Egfra and Egfrb, each of them being preferentially coexpressed with different subsets of Egfr ligands. This fish-specific occurrence of Egf receptor specialization offers unique opportunities to study the functions of different Egf receptor-ligand combinations and their biological outputs in vertebrates. Furthermore, our results strongly support the use of homologous ligands in future studies, as sufficient cross-specificity is very unlikely for this ligand/receptor system.},
  subject      = {Epidermaler Wachstumsfaktor-Rezeptor},
  language  = {en}
}
@article{HerpinBraaschKraeusslingetal.2010,
  author    = {Herpin, Amaury and Braasch, Ingo and Kraeussling, Michael and Schmidt, Cornelia and Thoma, Eva C. and Nakamura, Shuhei and Tanaka, Minoru and Schartl, Manfred},
  title     = {Transcriptional Rewiring of the Sex Determining dmrt1 Gene Duplicate by Transposable Elements},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68437},
  year      = {2010},
  abstract  = {Control and coordination of eukaryotic gene expression rely on transcriptional and posttranscriptional regulatory networks. Evolutionary innovations and adaptations often require rapid changes of such networks. It has long been hypothesized that transposable elements (TE) might contribute to the rewiring of regulatory interactions. More recently it emerged that TEs might bring in ready-to-use transcription factor binding sites to create alterations to the promoters by which they were captured. A process where the gene regulatory architecture is of remarkable plasticity is sex determination. While the more downstream components of the sex determination cascades are evolutionary conserved, the master regulators can switch between groups of organisms even on the interspecies level or between populations. In the medaka fish (Oryzias latipes) a duplicated copy of dmrt1, designated dmrt1bY or DMY, on the Y chromosome was shown to be the master regulator of male development, similar to Sry in mammals. We found that the dmrt1bY gene has acquired a new feedback downregulation of its expression. Additionally, the autosomal dmrt1a gene is also able to regulate transcription of its duplicated paralog by binding to a unique target Dmrt1 site nested within the dmrt1bY proximal promoter region. We could trace back this novel regulatory element to a highly conserved sequence within a new type of TE that inserted into the upstream region of dmrt1bY shortly after the duplication event. Our data provide functional evidence for a role of TEs in transcriptional network rewiring for sub- and/or neo-functionalization of duplicated genes. In the particular case of dmrt1bY, this contributed to create new hierarchies of sex-determining genes.},
  subject      = {Gen},
  language  = {en}
}
@article{MatosSucenaMachadoetal.2011,
  author    = {Matos, Isa and Sucena, {\`E}lio and Machado, Miguel P and Gardner, Rui and In{\´a}cio, {\^A}ngela and Schartl, Manfred and Coelho, Maria M},
  title     = {Ploidy mosaicism and allele-specific gene expression differences in the allopolyploid \(Squalius\) \(alburnoides\)},
  series = {BMC Genetics},
  volume    = {12},
  journal   = {BMC Genetics},
  number    = {101},
  doi       = {10.1186/1471-2156-12-101},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-142879},
  pages     = {1-10},
  year      = {2011},
  abstract  = {Background Squalius alburnoides is an Iberian cyprinid fish resulting from an interspecific hybridisation between Squalius pyrenaicus females (P genome) and males of an unknown Anaecypris hispanica- like species (A genome). S. alburnoides is an allopolyploid hybridogenetic complex, which makes it a likely candidate for ploidy mosaicism occurrence, and is also an interesting model to address questions about gene expression regulation and genomic interactions. Indeed, it was previously suggested that in S. alburnoides triploids (PAA composition) silencing of one of the three alleles (mainly of the P allele) occurs. However, not a whole haplome is inactivated but a more or less random inactivation of alleles varying between individuals and even between organs of the same fish was seen. In this work we intended to correlate expression differences between individuals and/or between organs to the occurrence of mosaicism, evaluating if mosaics could explain previous observations and its impact on the assessment of gene expression patterns. Results To achieve our goal, we developed flow cytometry and cell sorting protocols for this system generating more homogenous cellular and transcriptional samples. With this set-up we detected 10\% ploidy mosaicism within the S. alburnoides complex, and determined the allelic expression profiles of ubiquitously expressed genes (rpl8; gapdh and β-actin) in cells from liver and kidney of mosaic and non-mosaic individuals coming from different rivers over a wide geographic range. Conclusions Ploidy mosaicism occurs sporadically within the S. alburnoides complex, but in a frequency significantly higher than reported for other organisms. Moreover, we could exclude the influence of this phenomenon on the detection of variable allelic expression profiles of ubiquitously expressed genes (rpl8; gapdh and β-actin) in cells from liver and kidney of triploid individuals. Finally, we determined that the expression patterns previously detected only in a narrow geographic range is not a local restricted phenomenon but is pervasive in rivers where S. pyrenaicus is sympatric with S. alburnoides. We discuss mechanisms that could lead to the formation of mosaic S. alburnoides and hypothesise about a relaxation of the mechanisms that impose a tight control over mitosis and ploidy control in mixoploids."},
  language  = {en}
}
@article{WagnerFischerThomaetal.2011,
  author    = {Wagner, Toni U. and Fischer, Andreas and Thoma, Eva C. and Schartl, Manfred},
  title     = {CrossQuery : A Web Tool for Easy Associative Querying of Transcriptome Data},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-76088},
  year      = {2011},
  abstract  = {Enormous amounts of data are being generated by modern methods such as transcriptome or exome sequencing and microarray profiling. Primary analyses such as quality control, normalization, statistics and mapping are highly complex and need to be performed by specialists. Thereafter, results are handed back to biomedical researchers, who are then confronted with complicated data lists. For rather simple tasks like data filtering, sorting and cross-association there is a need for new tools which can be used by non-specialists. Here, we describe CrossQuery, a web tool that enables straight forward, simple syntax queries to be executed on transcriptome sequencing and microarray datasets. We provide deepsequencing data sets of stem cell lines derived from the model fish Medaka and microarray data of human endothelial cells. In the example datasets provided, mRNA expression levels, gene, transcript and sample identification numbers, GO-terms and gene descriptions can be freely correlated, filtered and sorted. Queries can be saved for later reuse and results can be exported to standard formats that allow copy-and-paste to all widespread data visualization tools such as Microsoft Excel. CrossQuery enables researchers to quickly and freely work with transcriptome and microarray data sets requiring only minimal computer skills. Furthermore, CrossQuery allows growing association of multiple datasets as long as at least one common point of correlated information, such as transcript identification numbers or GO-terms, is shared between samples. For advanced users, the object-oriented plug-in and event-driven code design of both server-side and client-side scripts allow easy addition of new features, data sources and data types.},
  subject      = {CrossQuery},
  language  = {en}
}
@article{KraeusslingWagnerSchartl2011,
  author    = {Kraeussling, Michael and Wagner, Toni Ulrich and Schartl, Manfred},
  title     = {Highly Asynchronous and Asymmetric Cleavage Divisions Accompany Early Transcriptional Activity in Pre-Blastula Medaka Embryos},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68906},
  year      = {2011},
  abstract  = {In the initial phase of development of fish embryos, a prominent and critical event is the midblastula transition (MBT). Before MBT cell cycle is rapid, highly synchronous and zygotic gene transcription is turned off. Only during MBT the cell cycle desynchronizes and transcription is activated. Multiple mechanisms, primarily the nucleocytoplasmic ratio, are supposed to control MBT activation. Unexpectedly, we find in the small teleost fish medaka (Oryzias latipes) that at very early stages, well before midblastula, cell division becomes asynchronous and cell volumes diverge. Furthermore, zygotic transcription is extensively activated already after the 64-cell stage. Thus, at least in medaka, the transition from maternal to zygotic transcription is uncoupled from the midblastula stage and not solely controlled by the nucleocytoplasmic ratio.},
  subject      = {Fische},
  language  = {en}
}
@article{WagnerFischerThomaetal.2011,
  author    = {Wagner, Toni U. and Fischer, Andreas and Thoma, Eva C. and Schartl, Manfred},
  title     = {CrossQuery: A Web Tool for Easy Associative Querying of Transcriptome Data},
  series = {PLoS ONE},
  volume    = {6},
  journal   = {PLoS ONE},
  number    = {12},
  doi       = {10.1371/journal.pone.0028990},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-134787},
  pages     = {e28990},
  year      = {2011},
  abstract  = {Enormous amounts of data are being generated by modern methods such as transcriptome or exome sequencing and microarray profiling. Primary analyses such as quality control, normalization, statistics and mapping are highly complex and need to be performed by specialists. Thereafter, results are handed back to biomedical researchers, who are then confronted with complicated data lists. For rather simple tasks like data filtering, sorting and cross-association there is a need for new tools which can be used by non-specialists. Here, we describe CrossQuery, a web tool that enables straight forward, simple syntax queries to be executed on transcriptome sequencing and microarray datasets. We provide deep-sequencing data sets of stem cell lines derived from the model fish Medaka and microarray data of human endothelial cells. In the example datasets provided, mRNA expression levels, gene, transcript and sample identification numbers, GO-terms and gene descriptions can be freely correlated, filtered and sorted. Queries can be saved for later reuse and results can be exported to standard formats that allow copy-and-paste to all widespread data visualization tools such as Microsoft Excel. CrossQuery enables researchers to quickly and freely work with transcriptome and microarray data sets requiring only minimal computer skills. Furthermore, CrossQuery allows growing association of multiple datasets as long as at least one common point of correlated information, such as transcript identification numbers or GO-terms, is shared between samples. For advanced users, the object-oriented plug-in and event-driven code design of both server-side and client-side scripts allow easy addition of new features, data sources and data types.},
  language  = {en}
}
@article{MenescalSchmidtLiedtkeetal.2012,
  author    = {Menescal, Luciana and Schmidt, Cornelia and Liedtke, Daniel and Schartl, Manfred},
  title     = {Liver hyperplasia after tamoxifen induction of Myc in a transgenic medaka model},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-75316},
  year      = {2012},
  abstract  = {Myc is a global transcriptional regulator and one of the most frequently overexpressed oncoproteins in human tumors. It is well established that activation of Myc leads to enhanced cell proliferation but can also lead to increased apoptosis. The use of animal models expressing deregulated levels of Myc has helped to both elucidate its function in normal cells and give insight into how Myc initiates and maintains tumorigenesis. Analyses of the medaka (Oryzias latipes) genome uncovered the unexpected presence of two Myc gene copies in this teleost species. Comparison of these Myc versions to other vertebrate species revealed that one gene, myc17, differs by the loss of some conserved regulatory protein motifs present in all other known Myc genes. To investigate how such differences might affect the basic biological functions of Myc, we generated a tamoxifeninducible in vivo model utilizing a natural, fish-specific Myc gene. Using this model we show that, when activated, Myc17 leads to increased proliferation and to apoptosis in a dose-dependent manner, similar to human Myc. We have also shown that long-term Myc17 activation triggers liver hyperplasia in adult fish, allowing this newly established transgenic medaka model to be used to study the transition from hyperplasia to liver cancer and to identify Myc-induced tumorigenesis modifiers.},
  subject      = {Biologie},
  language  = {en}
}
@article{SchartlKneitzWildeetal.2012,
  author    = {Schartl, Manfred and Kneitz, Susanne and Wilde, Brigitta and Wagner, Toni and Henkel, Christiaan V. and Spaink, Hermann P. and Meierjohann, Svenja},
  title     = {Conserved expression signatures between medaka and human pigment cell tumors},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-75848},
  year      = {2012},
  abstract  = {Aberrations in gene expression are a hallmark of cancer cells. Differential tumor-specific transcript levels of single genes or whole sets of genes may be critical for the neoplastic phenotype and important for therapeutic considerations or useful as biomarkers. As an approach to filter out such relevant expression differences from the plethora of changes noted in global expression profiling studies, we searched for changes of gene expression levels that are conserved. Transcriptomes from massive parallel sequencing of different types of melanoma from medaka were generated and compared to microarray datasets from zebrafish and human melanoma. This revealed molecular conservation at various levels between fish models and human tumors providing a useful strategy for identifying expression signatures strongly associated with disease phenotypes and uncovering new melanoma molecules.},
  subject      = {Biologie},
  language  = {en}
}
@article{ThomaWischmeyerOffenetal.2012,
  author    = {Thoma, Eva C. and Wischmeyer, Erhard and Offen, Nils and Maurus, Katja and Sir{\´e}n, Anna-Leena and Schartl, Manfred and Wagner, Toni U.},
  title     = {Ectopic expression of Neurogenin 2 alone is sufficient to induce differentiation of embryonic stem cells into mature neurons},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-75862},
  year      = {2012},
  abstract  = {Recent studies show that combinations of defined key developmental transcription factors (TFs) can reprogram somatic cells to pluripotency or induce cell conversion of one somatic cell type to another. However, it is not clear if single genes can define a cells identity and if the cell fate defining potential of TFs is also operative in pluripotent stem cells in vitro. Here, we show that ectopic expression of the neural TF Neurogenin2 (Ngn2) is sufficient to induce rapid and efficient differentiation of embryonic stem cells (ESCs) into mature glutamatergic neurons. Ngn2-induced neuronal differentiation did not require any additional external or internal factors and occurred even under pluripotency-promoting conditions. Differentiated cells displayed neuron-specific morphology, protein expression, and functional features, most importantly the generation of action potentials and contacts with hippocampal neurons. Gene expression analyses revealed that Ngn2-induced in vitro differentiation partially resembled neurogenesis in vivo, as it included specific activation of Ngn2 target genes and interaction partners. These findings demonstrate that a single gene is sufficient to determine cell fate decisions of uncommitted stem cells thus giving insights into the role of key developmental genes during lineage commitment. Furthermore, we present a promising tool to improve directed differentiation strategies for applications in both stem cell research and regenerative medicine.},
  subject      = {Physiologie},
  language  = {en}
}
@article{KangSchartlWalteretal.2013,
  author    = {Kang, Ji Hyoun and Schartl, Manfred and Walter, Ronald B. and Meyer, Axel},
  title     = {Comprehensive phylogenetic analysis of all species of swordtails and platies (Pisces: Genus Xiphophorus) uncovers a hybrid origin of a swordtail fish, Xiphophorus monticolus, and demonstrates that the sexually selected sword originated in the ancestral lineage of the genus, but was lost again secondarily},
  series = {BMC Evolutionary Biology},
  volume    = {13},
  journal   = {BMC Evolutionary Biology},
  number    = {25},
  issn      = {1471-2148},
  doi       = {10.1186/1471-2148-13-25},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-121853},
  year      = {2013},
  abstract  = {Background: Males in some species of the genus Xiphophorus, small freshwater fishes from Meso-America, have an extended caudal fin, or sword - hence their common name "swordtails". Longer swords are preferred by females from both sworded and - surprisingly also, non-sworded (platyfish) species that belong to the same genus. Swordtails have been studied widely as models in research on sexual selection. Specifically, the pre-existing bias hypothesis was interpreted to best explain the observed bias of females in presumed ancestral lineages of swordless species that show a preference for assumed derived males with swords over their conspecific swordless males. However, many of the phylogenetic relationships within this genus still remained unresolved. Here we construct a comprehensive molecular phylogeny of all 26 known Xiphophorus species, including the four recently described species (X. kallmani, X. mayae, X. mixei and X. monticolus). We use two mitochondrial and six new nuclear markers in an effort to increase the understanding of the evolutionary relationships among the species in this genus. Based on the phylogeny, the evolutionary history and character state evolution of the sword was reconstructed and found to have originated in the common ancestral lineage of the genus Xiphophorus and that it was lost again secondarily. Results: We estimated the evolutionary relationships among all known species of the genus Xiphophorus based on the largest set of DNA markers so far. The phylogeny indicates that one of the newly described swordtail species, Xiphophorus monticolus, is likely to have arisen through hybridization since it is placed with the southern platyfish in the mitochondrial phylogeny, but with the southern swordtails in the nuclear phylogeny. Such discordance between these two types of markers is a strong indication for a hybrid origin. Additionally, by using a maximum likelihood approach the possession of the sexually selected sword trait is shown to be the most likely ancestral state for the genus Xiphophorus. Further, we provide a well supported estimation of the phylogenetic relationships between the previously unresolved northern swordtail groups. Conclusions: This comprehensive molecular phylogeny of the entire genus Xiphophorus provides evidence that a second swordtail species, X. monticolus, arose through hybridization. Previously, we demonstrated that X. clemenciae, another southern swordtail species, arose via hybridization. These findings highlight the potential key role of hybridization in the evolution of this genus and suggest the need for further investigations into how hybridization contributes to speciation more generally.},
  language  = {en}
}
@article{YanHongChenetal.2013,
  author    = {Yan, Yan and Hong, Ni and Chen, Tiansheng and Li, Mingyou and Wang, Tiansu and Guan, Guijun and Qiao, Yongkang and Chen, Songlin and Schartl, Manfred and Li, Chang-Ming and Hong, Yunhan},
  title     = {p53 Gene Targeting by Homologous Recombination in Fish ES Cells},
  series = {PLoS One},
  volume    = {8},
  journal   = {PLoS One},
  number    = {3},
  doi       = {10.1371/journal.pone.0059400},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-133416},
  pages     = {e59400},
  year      = {2013},
  abstract  = {Background: Gene targeting (GT) provides a powerful tool for the generation of precise genetic alterations in embryonic stem (ES) cells to elucidate gene function and create animal models for human diseases. This technology has, however, been limited to mouse and rat. We have previously established ES cell lines and procedures for gene transfer and selection for homologous recombination (HR) events in the fish medaka (Oryzias latipes). Methodology and Principal Findings: Here we report HR-mediated GT in this organism. We designed a GT vector to disrupt the tumor suppressor gene p53 (also known as tp53). We show that all the three medaka ES cell lines, MES1 similar to MES3, are highly proficient for HR, as they produced detectable HR without drug selection. Furthermore, the positive-negative selection (PNS) procedure enhanced HR by similar to 12 folds. Out of 39 PNS-resistant colonies analyzed, 19 (48.7\%) were positive for GT by PCR genotyping. When 11 of the PCR-positive colonies were further analyzed, 6 (54.5\%) were found to be bona fide homologous recombinants by Southern blot analysis, sequencing and fluorescent in situ hybridization. This produces a high efficiency of up to 26.6\% for p53 GT under PNS conditions. We show that p53 disruption and long-term propagation under drug selection conditions do not compromise the pluripotency, as p53-targeted ES cells retained stable growth, undifferentiated phenotype, pluripotency gene expression profile and differentiation potential in vitro and in vivo. Conclusions: Our results demonstrate that medaka ES cells are proficient for HR-mediated GT, offering a first model organism of lower vertebrates towards the development of full ES cell-based GT technology.},
  language  = {en}
}
@article{SchulSchmittRegnerietal.2013,
  author    = {Schul, Daniela and Schmitt, Alexandra and Regneri, Janine and Schartl, Manfred and Wagner, Toni Ulrich},
  title     = {Bursted BMP Triggered Receptor Kinase Activity Drives Smad1 Mediated Long-Term Target Gene Oscillation in c2c12 Cells},
  series = {PLoS ONE},
  volume    = {8},
  journal   = {PLoS ONE},
  number    = {4},
  doi       = {10.1371/journal.pone.0059442},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-130131},
  pages     = {e59442},
  year      = {2013},
  abstract  = {Bone Morphogenetic Proteins (BMPs) are important growth factors that regulate many cellular processes. During embryogenesis they act as morphogens and play a critical role during organ development. They influence cell fates via concentration-gradients in the embryos where cells transduce this extracellular information into gene expression profiles and cell fate decisions. How receiving cells decode and quantify BMP2/4 signals is hardly understood. There is little data on the quantitative relationships between signal input, transducing molecules, their states and location, and ultimately their ability to integrate graded systemic inputs and generate qualitative responses. Understanding this signaling network on a quantitative level should be considered a prerequisite for efficient pathway modulation, as the BMP pathway is a prime target for therapeutic invention. Hence, we quantified the spatial distribution of the main signal transducer of the BMP2/4 pathway in response to different types and levels of stimuli in c2c12 cells. We found that the subcellular localization of Smad1 is independent of ligand concentration. In contrast, Smad1 phosphorylation levels relate proportionally to BMP2 ligand concentrations and they are entirely located in the nucleus. Interestingly, we found that BMP2 stimulates target gene expression in non-linear, wave-like forms. Amplitudes showed a clear concentration-dependency, for sustained and transient stimulation. We found that even burst-stimulation triggers gene-expression wave-like modulations that are detectable for at least 30 h. Finally, we show here that target gene expression oscillations depend on receptor kinase activity, as the kinase drives further expression pulses without receptor reactivation and the target gene expression breaks off after inhibitor treatment in c2c12 cells.},
  language  = {en}
}
@article{SchartlWalterShenetal.2013,
  author    = {Schartl, Manfred and Walter, Ronald B. and Shen, Yingjia and Garcia, Tzintzuni and Catchen, Julian and Amores, Angel and Braasch, Ingo and Chalopin, Domitille and Volff, Jean-Nicolas and Lesch, Klaus-Peter and Bisazza, Angelo and Minx, Pat and Hillier, LaDeana and Wilson, Richard K. and F{\"u}rstenberg, Susan and Boore, Jeffrey and Searle, Steve and Postlethwait, John H. and Warren, Wesley C.},
  title     = {The genome of the platyfish, Xiphophorus maculatus, provides insights into evolutionary adaptation and several complex traits},
  series = {Nature Genetics},
  volume    = {45},
  journal   = {Nature Genetics},
  number    = {5},
  doi       = {10.1038/ng.2604},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-132152},
  pages     = {567-572},
  year      = {2013},
  abstract  = {Several attributes intuitively considered to be typical mammalian features, such as complex behavior, live birth and malignant disease such as cancer, also appeared several times independently in lower vertebrates. The genetic mechanisms underlying the evolution of these elaborate traits are poorly understood. The platyfish, X. maculatus, offers a unique model to better understand the molecular biology of such traits. We report here the sequencing of the platyfish genome. Integrating genome assembly with extensive genetic maps identified an unexpected evolutionary stability of chromosomes in fish, in contrast to in mammals. Genes associated with viviparity show signatures of positive selection, identifying new putative functional domains and rare cases of parallel evolution. We also find that genes implicated in cognition show an unexpectedly high rate of duplicate gene retention after the teleost genome duplication event, suggesting a hypothesis for the evolution of the behavioral complexity in fish, which exceeds that found in amphibians and reptiles.},
  language  = {en}
}
@article{HerpinAdolfiNicoletal.2013,
  author    = {Herpin, Amaury and Adolfi, Mateus C. and Nicol, Barbara and Hinzmann, Maria and Schmidt, Cornelia and Klughammer, Johanna and Engel, Mareen and Tanaka, Minoru and Guiguen, Yann and Schartl, Manfred},
  title     = {Divergent Expression Regulation of Gonad Development Genes in Medaka Shows Incomplete Conservation of the Downstream Regulatory Network of Vertebrate Sex Determination},
  series = {Molecular Biology and Evolution},
  volume    = {30},
  journal   = {Molecular Biology and Evolution},
  number    = {10},
  doi       = {10.1093/molbev/mst130},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-132262},
  pages     = {2328-2346},
  year      = {2013},
  abstract  = {Genetic control of male or female gonad development displays between different groups of organisms a remarkable diversity of "master sex-determining genes" at the top of the genetic hierarchies, whereas downstream components surprisingly appear to be evolutionarily more conserved. Without much further studies, conservation of sequence has been equalized to conservation of function. We have used the medaka fish to investigate the generality of this paradigm. In medaka, the master male sex-determining gene is dmrt1bY, a highly conserved downstream regulator of sex determination in vertebrates. To understand its function in orchestrating the complex gene regulatory network, we have identified targets genes and regulated pathways of Dmrt1bY. Monitoring gene expression and interactions by transgenic fluorescent reporter fish lines, in vivo tissue-chromatin immunoprecipitation and in vitro gene regulation assays revealed concordance but also major discrepancies between mammals and medaka, notably amongst spatial, temporal expression patterns and regulations of the canonical Hedgehog and R-spondin/Wnt/Follistatin signaling pathways. Examination of Foxl2 protein distribution in the medaka ovary defined a new subpopulation of theca cells, where ovarian-type aromatase transcriptional regulation appears to be independent of Foxl2. In summary, these data show that the regulation of the downstream regulatory network of sex determination is less conserved than previously thought.},
  language  = {en}
}
@article{ForconiCanapaBaruccaetal.2013,
  author    = {Forconi, Mariko and Canapa, Adriana and Barucca, Marco and Biscotti, Maria A. and Capriglione, Teresa and Buonocore, Francesco and Fausto, Anna M. and Makapedua, Daisy M. and Pallavicini, Alberto and Gerdol, Marco and De Moro, Gianluca and Scapigliati, Giuseppe and Olmo, Ettore and Schartl, Manfred},
  title     = {Characterization of Sex Determination and Sex Differentiation Genes in Latimeria},
  series = {PLoS ONE},
  volume    = {8},
  journal   = {PLoS ONE},
  number    = {4},
  doi       = {10.1371/journal.pone.0056006},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-130995},
  pages     = {e56006},
  year      = {2013},
  abstract  = {Genes involved in sex determination and differentiation have been identified in mice, humans, chickens, reptiles, amphibians and teleost fishes. However, little is known of their functional conservation, and it is unclear whether there is a common set of genes shared by all vertebrates. Coelacanths, basal Sarcopterygians and unique "living fossils", could help establish an inventory of the ancestral genes involved in these important developmental processes and provide insights into their components. In this study 33 genes from the genome of Latimeria chalumnae and from the liver and testis transcriptomes of Latimeria menadoensis, implicated in sex determination and differentiation, were identified and characterized and their expression levels measured. Interesting findings were obtained for GSDF, previously identified only in teleosts and now characterized for the first time in the sarcopterygian lineage; FGF9, which is not found in teleosts; and DMRT1, whose expression in adult gonads has recently been related to maintenance of sexual identity. The gene repertoire and testis-specific gene expression documented in coelacanths demonstrate a greater similarity to modern fishes and point to unexpected changes in the gene regulatory network governing sexual development.},
  language  = {en}
}
@article{HaydnHufnagelGrimmetal.2014,
  author    = {Haydn, Johannes M. and Hufnagel, Anita and Grimm, Johannes and Maurus, Katja and Schartl, Manfred and Meierjohann, Svenja},
  title     = {The MAPK pathway as an apoptosis enhancer in melanoma},
  series = {Oncotarget},
  volume    = {5},
  journal   = {Oncotarget},
  number    = {13},
  issn      = {1949-2553},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-120649},
  pages     = {5040-53},
  year      = {2014},
  abstract  = {Inhibition of RAF/MEK/ERK signaling is beneficial for many patients with BRAFV600E-mutated melanoma. However, primary and secondary resistances restrict long-lasting therapy success. Combination therapies are therefore urgently needed. Here, we evaluate the cellular effect of combining a MEK inhibitor with a genotoxic apoptosis inducer. Strikingly, we observed that an activated MAPK pathway promotes in several melanoma cell lines the pro-apoptotic response to genotoxic stress, and MEK inhibition reduces intrinsic apoptosis. This goes along with MEK inhibitor induced increased RAS and P-AKT levels. The protective effect of the MEK inhibitor depends on PI3K signaling, which prevents the induction of pro-apoptotic PUMA that mediates apoptosis after DNA damage. We could show that the MEK inhibitor dependent feedback loop is enabled by several factors, including EGF receptor and members of the SPRED family. The simultaneous knockdown of SPRED1 and SPRED2 mimicked the effects of MEK inhibitor such as PUMA repression and protection from apoptosis. Our data demonstrate that MEK inhibition of BRAFV600E-positive melanoma cells can protect from genotoxic stress, thereby achieving the opposite of the intended anti-tumorigenic effect of the combination of MEK inhibitor with inducers of intrinsic apoptosis.},
  language  = {en}
}
@article{Schartl2014,
  author    = {Schartl, Manfred},
  title     = {Beyond the zebrafish: diverse fish species for modeling human disease},
  series = {Disease Models \& Mechanisms},
  volume    = {7},
  journal   = {Disease Models \& Mechanisms},
  number    = {2},
  issn      = {1754-8411},
  doi       = {10.1242/dmm.012245},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-119919},
  year      = {2014},
  abstract  = {In recent years, zebrafish, and to a lesser extent medaka, have become widely used small animal models for human diseases. These organisms have convincingly demonstrated the usefulness of fish for improving our understanding of the molecular and cellular mechanisms leading to pathological conditions, and for the development of new diagnostic and therapeutic tools. Despite the usefulness of zebrafish and medaka in the investigation of a wide spectrum of traits, there is evidence to suggest that other fish species could be better suited for more targeted questions. With the emergence of new, improved sequencing technologies that enable genomic resources to be generated with increasing efficiency and speed, the potential of non-mainstream fish species as disease models can now be explored. A key feature of these fish species is that the pathological condition that they model is often related to specific evolutionary adaptations. By exploring these adaptations, new disease-causing and disease-modifier genes might be identified; thus, diverse fish species could be exploited to better understand the complexity of disease processes. In addition, non-mainstream fish models could allow us to study the impact of environmental factors, as well as genetic variation, on complex disease phenotypes. This Review will discuss the opportunities that such fish models offer for current and future biomedical research.},
  language  = {en}
}
@article{TomaszkiewiczChalopinSchartletal.2014,
  author    = {Tomaszkiewicz, Marta and Chalopin, Domitille and Schartl, Manfred and Galiana, Delphine and Volff, Jean-Nicolas},
  title     = {A multicopy Y-chromosomal SGNH hydrolase gene expressed in the testis of the platyfish has been captured and mobilized by a Helitron transposon},
  series = {BMC Genetics},
  volume    = {15},
  journal   = {BMC Genetics},
  number    = {44},
  doi       = {10.1186/1471-2156-15-44},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-116746},
  year      = {2014},
  abstract  = {Background: Teleost fish present a high diversity of sex determination systems, with possible frequent evolutionary turnover of sex chromosomes and sex-determining genes. In order to identify genes involved in male sex determination and differentiation in the platyfish Xiphophorus maculatus, bacterial artificial chromosome contigs from the sex-determining region differentiating the Y from the X chromosome have been assembled and analyzed. Results: A novel three-copy gene called teximY (for testis-expressed in Xiphophorus maculatus on the Y) was identified on the Y but not on the X chromosome. A highly related sequence called texim1, probably at the origin of the Y-linked genes, as well as three more divergent texim genes were detected in (pseudo) autosomal regions of the platyfish genome. Texim genes, for which no functional data are available so far in any organism, encode predicted esterases/lipases with a SGNH hydrolase domain. Texim proteins are related to proteins from very different origins, including proteins encoded by animal CR1 retrotransposons, animal platelet-activating factor acetylhydrolases (PAFah) and bacterial hydrolases. Texim gene distribution is patchy in animals. Texim sequences were detected in several fish species including killifish, medaka, pufferfish, sea bass, cod and gar, but not in zebrafish. Texim-like genes are also present in Oikopleura (urochordate), Amphioxus (cephalochordate) and sea urchin (echinoderm) but absent from mammals and other tetrapods. Interestingly, texim genes are associated with a Helitron transposon in different fish species but not in urochordates, cephalochordates and echinoderms, suggesting capture and mobilization of an ancestral texim gene in the bony fish lineage. RT-qPCR analyses showed that Y-linked teximY genes are preferentially expressed in testis, with expression at late stages of spermatogenesis (late spermatids and spermatozeugmata). Conclusions: These observations suggest either that TeximY proteins play a role in Helitron transposition in the male germ line in fish, or that texim genes are spermatogenesis genes mobilized and spread by transposable elements in fish genomes.},
  language  = {en}
}