@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{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{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} } @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{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{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{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{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{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} } @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{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{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{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{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{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} } @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} } @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{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{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{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{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{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{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{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{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{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{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} } @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{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{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{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{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{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{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} } @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{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{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{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{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{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{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{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{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{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{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{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{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{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{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{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} }