TY - CHAP A1 - Schartl, A. A1 - Schartl, Manfred A1 - Anders, F. T1 - Phenotypic conversion of malignant melanoma to benign melanoma and vice versa in Xiphophorus N2 - No abstract available. KW - Schwertkärpfling KW - Krebs Y1 - 1981 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-86662 ER - TY - CHAP A1 - Anders, F. A1 - Scholl, E. A1 - Schartl, Manfred T1 - Environmental and hereditary factors in the causation of neoplasia, based on studies of the Xiphophorus fish melanoma system N2 - 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. KW - Schwertkärpfling KW - Gen KW - Umweltfaktor KW - Tumor Y1 - 1981 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-86402 ER - TY - CHAP A1 - Anders, Fritz A1 - Schartl, Manfred A1 - Barnekow, Angelika T1 - Xiphophorus as an in vivo model for studies on oncogenes N2 - 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. KW - Schwertkärpfling KW - In vivo KW - Onkogen Y1 - 1984 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-86398 ER - TY - CHAP A1 - Adam, D. A1 - Schartl, A. A1 - Andexinger, S. A1 - Hölter, S. A1 - Wilde, B. A1 - Schartl, Manfred T1 - Genetic factors in tumour formation: The melanoma-inducing gene of Xiphophorus N2 - No abstract available. KW - Humangenetik KW - Tumor KW - Entstehung Y1 - 1991 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-86388 ER - TY - CHAP A1 - Epplen, J. T. A1 - Ammer, H. A1 - Epplen, C. A1 - Kammerbauer, C. A1 - Mitreiter, R. A1 - Roewer, L. A1 - Schwaiger, W. A1 - Steimle, V. A1 - Zischler, H. A1 - Albert, E. A1 - Andreas, A. A1 - Beyermann, B. A1 - Meyer, W. A1 - Buitkamp, J. A1 - Nanda, I. A1 - Nürnberg, P. A1 - Pena, S. D. J. A1 - Pöche, H. A1 - Sprecher, W. A1 - Schartl, Manfred A1 - Weising, K. A1 - Yassouridis, A. T1 - Oligonucleotide fingerprinting using simple repeat motifs: a convenient, ubiquitously applicable method to detect hypervariability for multiple purposes N2 - 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. KW - DNS KW - Fingerprint-Verfahren Y1 - 1991 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-86371 ER - TY - JOUR A1 - Schartl, Manfred A1 - Nanda, Indrajit A1 - Schlupp, Ingo A1 - Parzefall, Jakob A1 - Schmid, Michael A1 - Epplen, Jörg T. T1 - Genetic variation in the clonal vertebrate Poecilia formosa is limited to few truly hypervariable loci N2 - No abstract available. KW - Amazon Molly Y1 - 1990 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-86359 ER - TY - JOUR A1 - Schartl, Manfred A1 - Erbelding-Denk, Claudia A1 - Nanda, Indrajit A1 - Schmid, Michael A1 - Schröder, Johannes Horst A1 - Epplen, Jörg T. T1 - Mating success of subordinate males in a poeciliid fish species, Limia perugiae N2 - No abstract available. KW - Lebendgebärende Zahnkarpfen KW - Perugia-Kärpfling Y1 - 1991 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-86349 ER - TY - JOUR A1 - Maueler, W. A1 - Barnekow, A. A1 - Eigenbrodt, E. A1 - Raulf, F. A1 - Falk, H. F. A1 - Telling, A. A1 - Schartl, Manfred T1 - Different regulation of oncogene expression in tumor and embryonal cells of Xiphophorus N2 - 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. KW - Schwertkärpfling KW - Tumorzelle Y1 - 1988 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-86240 ER - TY - JOUR A1 - Mäueler, Winfried A1 - Raulf, Friedrich A1 - Schartl, Manfred T1 - Expression of proto-oncogenes in embryonic, adult, and transformed tissue of Xiphophorus (Teleostei: Poeciliidae) N2 - 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. KW - Schwertkärpfling KW - Protoonkogen KW - Gewebe Y1 - 1988 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-86233 ER - TY - JOUR A1 - Schartl, Manfred A1 - Barnekow, Angelika T1 - The expression in eukaryotes of a tyrosine kinase which is reactive with pp60v-src antibodies N2 - 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. KW - Protein-Tyrosin-Kinasen KW - Eukaryoten Y1 - 1982 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-86208 ER - TY - JOUR A1 - Schartl, Manfred A1 - Holstein, Thomas A1 - Robertson, Scott M. A1 - Barnekow, Angelika T1 - Preferential expression of a pp60c-src related protein tyrosine kinase activity in nerve cells of the early metazoan Hydra (Coelenterates) N2 - 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. KW - Protein-Tyrosin-Kinasen KW - Nervenzelle KW - Süßwasserpolypen Y1 - 1989 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-86179 ER - TY - JOUR A1 - Schartl, Angelika A1 - Schartl, Manfred T1 - Genes and cancer: Molecular biology of the melanoma oncogene of Xiphophorus N2 - No abstract available. KW - Schwertkärpfling KW - Krebs Y1 - 1990 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-72670 ER - TY - CHAP A1 - Altschmied, Joachim A1 - Schartl, Manfred T1 - Genetics and molecular biology of tumour formation in Xiphophorus N2 - No abstract available. KW - Schwertkärpfling KW - Tumor KW - Entstehung KW - Molekularbiologie KW - Genetik Y1 - 1994 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-69752 ER - TY - CHAP A1 - Peter, R. U. A1 - Schartl, Manfred A1 - Anders, F. A1 - Duncker, H.-R. T1 - Pigment pattern formation during embryogenesis in Xiphophorus N2 - No abstract available. KW - Schwertkärpfling KW - Embryonalentwicklung KW - Pigmentmuster Y1 - 1985 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-69370 ER - TY - CHAP A1 - Riehl, Rüdiger A1 - Schartl, Manfred A1 - Anders, Fritz T1 - An ultrastructural study of melanoma in Xiphophorus N2 - 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. KW - Schwertkärpfling KW - Krebs KW - Ultrastruktur Y1 - 1985 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-70978 ER - TY - CHAP A1 - Schartl, Manfred A1 - Mäueler, Winfried A1 - Raulf, Friedrich A1 - Robertson, Scott M. T1 - Molecular aspects of melanoma formation in Xiphophorus N2 - No abstract available. KW - Schwertkärpfling KW - Krebs Y1 - 1988 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-72689 ER - TY - JOUR A1 - Anders, F. A1 - Schartl, Manfred A1 - Barnekow, A. A1 - Schmidt, C. R. A1 - Luke, W. A1 - Jaenel-Dess, G. A1 - Anders, A. T1 - The genes that carcinogens act upon N2 - No abstract available. KW - Onkogen Y1 - 1985 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-72704 ER - TY - JOUR A1 - Meyer, Manfred K. A1 - Schartl, Manfred T1 - Pseudotropheus (Maylandia) hajomaylandi n. sp., a new taxon from Lake Malawi T1 - Pseudotropheus (Maylandia) hajomaylandi n. sp. un nouveau taxon du Lac Malawi N2 - 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. KW - Buntbarsche KW - Njassasee Y1 - 1984 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-70989 ER - TY - CHAP A1 - Anders, F. A1 - Schartl, Manfred A1 - Scholl, E. T1 - Evaluation of environmental and hereditary factors in carcinogenesis, based on studies in Xiphophorus N2 - 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. KW - Schwertkärpfling KW - Gen KW - Umweltfaktor KW - Carcinogenese Y1 - 1981 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-72741 ER - TY - JOUR A1 - Cavari, Benzion A1 - Funkenstein, Bruria A1 - Chen, Thomas T. A1 - Gonzalez-Villasenor, Lucia Irene A1 - Schartl, Manfred T1 - 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 N2 - 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. KW - Goldbrasse KW - Somatotropin KW - Wachstum KW - Transgene Tiere Y1 - 1993 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-69765 ER - TY - JOUR A1 - Malitschek, B. A1 - Schartl, Manfred T1 - Rapid identification of recombinant baculoviruses using PCR N2 - no abstract available KW - PCR Y1 - 1991 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-80328 ER - TY - JOUR A1 - Schlupp, I. A1 - Parzefall, J. A1 - Schartl, Manfred T1 - Male mate choice in mixed bisexual/-unisexual breeding complexes of Poecilia (Teleostei: Poeciliidae) N2 - 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. KW - Poecilia (Teleostei: Poeciliidae) Y1 - 1991 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-80309 ER - TY - JOUR A1 - Ottilie, S. A1 - Raulf, F. A1 - Barnekow, A. A1 - Hannig, G. A1 - Schartl, Manfred T1 - Multiple src-related kinase genes, srk1-4, in the fresh water sponge Spongilla lacustris N2 - 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. KW - Spongilla lacustris Y1 - 1992 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-80282 ER - TY - JOUR A1 - Thoma, Eva C. A1 - Wischmeyer, Erhard A1 - Offen, Nils A1 - Maurus, Katja A1 - Sirén, Anna-Leena A1 - Schartl, Manfred A1 - Wagner, Toni U. T1 - Ectopic expression of Neurogenin 2 alone is sufficient to induce differentiation of embryonic stem cells into mature neurons N2 - 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. KW - Physiologie Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-75862 ER - TY - JOUR A1 - Schartl, Manfred A1 - Kneitz, Susanne A1 - Wilde, Brigitta A1 - Wagner, Toni A1 - Henkel, Christiaan V. A1 - Spaink, Hermann P. A1 - Meierjohann, Svenja T1 - Conserved expression signatures between medaka and human pigment cell tumors N2 - 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. KW - Biologie Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-75848 ER - TY - JOUR A1 - Menescal, Luciana A1 - Schmidt, Cornelia A1 - Liedtke, Daniel A1 - Schartl, Manfred T1 - Liver hyperplasia after tamoxifen induction of Myc in a transgenic medaka model N2 - 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. KW - Biologie Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-75316 ER - TY - JOUR A1 - Wagner, Toni U. A1 - Fischer, Andreas A1 - Thoma, Eva C. A1 - Schartl, Manfred T1 - CrossQuery : A Web Tool for Easy Associative Querying of Transcriptome Data N2 - 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. KW - CrossQuery Y1 - 2011 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-76088 ER - TY - JOUR A1 - Meierjohann, Svenja A1 - Hufnagel, Anita A1 - Wende, Elisabeth A1 - Kleinschmidt, Markus A. A1 - Wolf, Katarina A1 - Friedl, Peter A1 - Gaubatz, Stefan A1 - Schartl, Manfred T1 - MMP13 mediates cell cycle progression in melanocytes and melanoma cells: in vitro studies of migration and proliferation N2 - 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. KW - Medizin Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68335 ER - TY - JOUR A1 - Schartl, Manfred A1 - Adam, Dieter T1 - Molecular cloning, structural characterization, and analysis of transcription of the melanoma oncogene of xiphophorus N2 - No abstract available KW - Physiologische Chemie Y1 - 1992 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61989 ER - TY - JOUR A1 - Lubjuhn, T. A1 - Schartl, Manfred A1 - Epplen, J. T. T1 - Methodik und Anwendungsgebiete des genetischen Fingerabdruckverfahrens N2 - No abstract available KW - Physiologische Chemie Y1 - 1994 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61978 ER - TY - CHAP A1 - Gotz, R. A1 - Schartl, Manfred T1 - The conservation of neurotrophic factors during vertebrate evolution N2 - No abstract available KW - Physiologische Chemie Y1 - 1994 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61964 ER - TY - JOUR A1 - Schartl, A. A1 - Dimitrijevic, N. A1 - Schartl, Manfred T1 - Evolutionary origin and molecular biology of the melanoma-inducing oncogene of Xiphophorus N2 - No abstract available KW - Physiologische Chemie Y1 - 1994 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61954 ER - TY - JOUR A1 - Barnekow, A. A1 - Schartl, Manfred A1 - Anders, F. A1 - Bauer, H. T1 - Identification of a fish protein associated with a kinase activity and related to the Rous sarcoma virus transforming protein N2 - No abstract available KW - Physiologische Chemie Y1 - 1982 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61946 ER - TY - JOUR A1 - Schartl, Manfred A1 - Barnekow, A. A1 - Bauer, H. A1 - Anders, F. T1 - Correlations of inheritance and expression between a tumor gene and the cellular homolog of the Rous sarcoma virus-transforming gene in Xiphophorus N2 - No abstract available KW - Physiologische Chemie Y1 - 1982 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61937 ER - TY - JOUR A1 - Riehl, R. A1 - Schartl, Manfred A1 - Kollinger, G. T1 - Comparative studies on the ultrastructure of malignant melanoma in fish and human by freeze-etching and transmission electron microscopy N2 - 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. KW - Physiologische Chemie KW - Malignant melanoma KW - Fish KW - Human KW - Freeze-etching KW - Transmission electron microscopy Y1 - 1984 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61920 ER - TY - JOUR A1 - Riehl, R. A1 - Schartl, Manfred T1 - A Transmission Electron Microscopical and Freeze-Etch Study of Malignant-Melanoma in Fish N2 - No abstract available KW - Physiologische Chemie Y1 - 1984 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61916 ER - TY - JOUR A1 - Schartl, Manfred A1 - Barnekow, A. T1 - Cellular src gene product detected in the freshwater sponge Spongilla lacustris N2 - No abstract available KW - Physiologische Chemie Y1 - 1984 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61904 ER - TY - JOUR A1 - Schartl, Manfred A1 - Barnekow, A. T1 - Differential expression of the cellular src gene during vertebrate development N2 - No abstract available KW - Physiologische Chemie Y1 - 1984 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61893 ER - TY - JOUR A1 - Schartl, Manfred A1 - Schmidt, C. R. A1 - Anders, A. A1 - Barnekow, A. T1 - Elevated expression of the cellular src gene in tumors of differing etiologies in Xiphophorus N2 - No abstract available KW - Physiologische Chemie Y1 - 1985 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61889 ER - TY - JOUR A1 - Barnekow, A. A1 - Paul, E. A1 - Schartl, Manfred T1 - Expression of the c-src protooncogene in human skin tumors N2 - No abstract available KW - Physiologische Chemie Y1 - 1987 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61870 ER - TY - JOUR A1 - Barnekow, A. A1 - Schartl, Manfred T1 - Comparative studies on the src proto-oncogene and its gene product pp60\(^{c-src}\) in normal and neoplastic tissues of lower vertebrates N2 - No abstract available KW - Physiologische Chemie Y1 - 1987 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61869 ER - TY - JOUR A1 - Maueler, W. A1 - Eigenbrodt, E. A1 - Schartl, Manfred T1 - Intermediary metabolism of normal and tumorous tissue of Xiphophorus (Teleostei: Poeciliidae) N2 - No abstract available KW - Physiologische Chemie Y1 - 1987 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61855 ER - TY - JOUR A1 - Schartl, Manfred T1 - A sex chromosomal restriction-fragment-length marker linked to melanoma-determining Tu loci in Xiphophorus N2 - No abstract available KW - Physiologische Chemie Y1 - 1988 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61842 ER - TY - JOUR A1 - Schartl, Manfred A1 - Peter, R. U. T1 - Progressive growth of fish tumors after transplantation into thymus-aplastic (nu/nu) mice N2 - No abstract available KW - Physiologische Chemie Y1 - 1988 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61833 ER - TY - JOUR A1 - Adam, D. A1 - Wittbrodt, J. A1 - Telling, A. A1 - Schartl, Manfred T1 - RFLP for an EGF-receptor related gene associated with the melanoma oncogene locus of Xiphophorus maculatus N2 - No abstract available KW - Physiologische Chemie Y1 - 1988 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61822 ER - TY - JOUR A1 - Bernards, R. A1 - Schackleford, G. M. A1 - Gerber, M. R. A1 - Horowitz, J. M. A1 - Friend, S. H. A1 - Schartl, Manfred A1 - Bogenmann, E. A1 - Rapaport, J. M. A1 - Mcgee, T. A1 - Dryja, T. P. T1 - Structure and expression of the murine retinoblastoma gene and characterization of its encoded protein N2 - No abstract available KW - Physiologische Chemie Y1 - 1989 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61819 ER - TY - JOUR A1 - Wittbrodt, J. A1 - Adam, D. A1 - Malitschek, B. A1 - Maueler, W. A1 - Raulf, F. A1 - Telling, A. A1 - Robertson, M. A1 - Schartl, Manfred T1 - Novel putative receptor tyrosine kinase encoded by the melanoma-inducing Tu locus in Xiphophorus N2 - No abstract available KW - Physiologische Chemie Y1 - 1989 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61800 ER - TY - JOUR A1 - Raulf, F. A1 - Robertson, S. M. A1 - Schartl, Manfred T1 - Evolution of the neuron-specific alternative splicing product of the c-src proto-oncogene N2 - 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. KW - Physiologische Chemie KW - Xiphophorus KW - teleost flsh KW - polymerase KW - chain reaction KW - RT -PCR KW - mini-exon KW - pp6oc-src Y1 - 1989 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61796 ER - TY - JOUR A1 - Kraeussling, Michael A1 - Wagner, Toni Ulrich A1 - Schartl, Manfred T1 - Highly Asynchronous and Asymmetric Cleavage Divisions Accompany Early Transcriptional Activity in Pre-Blastula Medaka Embryos N2 - 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. KW - Fische KW - Embryo Y1 - 2011 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68906 ER - TY - JOUR A1 - Herpin, Amaury A1 - Braasch, Ingo A1 - Kraeussling, Michael A1 - Schmidt, Cornelia A1 - Thoma, Eva C. A1 - Nakamura, Shuhei A1 - Tanaka, Minoru A1 - Schartl, Manfred T1 - Transcriptional Rewiring of the Sex Determining dmrt1 Gene Duplicate by Transposable Elements N2 - 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. KW - Gen KW - dmrt1 KW - sex-determining gene Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68437 ER -