@article{KangManousakiFranchinietal.2015, author = {Kang, Ji Hyoun and Manousaki, Tereza and Franchini, Paolo and Kneitz, Susanne and Schartl, Manfred and Meyer, Axel}, title = {Transcriptomics of two evolutionary novelties: how to make a sperm-transfer organ out of an anal fin and a sexually selected "sword" out of a caudal fin}, series = {Ecology and Evolution}, volume = {5}, journal = {Ecology and Evolution}, number = {4}, doi = {10.1002/ece3.1390}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-144139}, pages = {848-864}, year = {2015}, abstract = {Swords are exaggerated male ornaments of swordtail fishes that have been of great interest to evolutionary biologists ever since Darwin described them in the Descent of Man (1871). They are a novel sexually selected trait derived from modified ventral caudal fin rays and are only found in the genus Xiphophorus. Another phylogenetically more widespread and older male trait is the gonopodium, an intromittent organ found in all poeciliid fishes, that is derived from a modified anal fin. Despite many evolutionary and behavioral studies on both traits, little is known so far about the molecular mechanisms underlying their development. By investigating transcriptomic changes (utilizing a RNA-Seq approach) in response to testosterone treatment in the swordtail fish, Xiphophorus hellerii, we aimed to better understand the architecture of the gene regulatory networks underpinning the development of these two evolutionary novelties. Large numbers of genes with tissue-specific expression patterns were identified. Among the sword genes those involved in embryonic organ development, sexual character development and coloration were highly expressed, while in the gonopodium rather more morphogenesis-related genes were found. Interestingly, many genes and genetic pathways are shared between both developing novel traits derived from median fins: the sword and the gonopodium. Our analyses show that a larger set of gene networks was co-opted during the development and evolution of the older gonopodium than in the younger, and morphologically less complex trait, the sword. We provide a catalog of candidate genes for future efforts to dissect the development of those sexually selected exaggerated male traits in swordtails.}, language = {en} } @article{LamatschAdolfssonSenioretal.2015, author = {Lamatsch, Dunja K. and Adolfsson, Sofia and Senior, Alistair M. and Christiansen, Guntram and Pichler, Maria and Ozaki, Yuichi and Smeds, Linnea and Schartl, Manfred and Nakagawa, Shinichi}, title = {A transcriptome derived female-specific marker from the invasive Western mosquitofish (Gambusia affinis)}, series = {PLoS ONE}, volume = {10}, journal = {PLoS ONE}, number = {2}, doi = {10.1371/journal.pone.0118214}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-144004}, pages = {e0118214}, year = {2015}, abstract = {Sex-specific markers are a prerequisite for understanding reproductive biology, genetic factors involved in sex differences, mechanisms of sex determination, and ultimately the evolution of sex chromosomes. The Western mosquitofish, Gambusia affinis, may be considered a model species for sex-chromosome evolution, as it displays female heterogamety (ZW/ZZ), and is also ecologically interesting as a worldwide invasive species. Here, de novo RNA-sequencing on the gonads of sexually mature G. affinis was used to identify contigs that were highly transcribed in females but not in males (i.e., transcripts with ovary-specific expression). Subsequently, 129 primer pairs spanning 79 contigs were tested by PCR to identify sex-specific transcripts. Of those primer pairs, one female-specific DNA marker was identified, Sanger sequenced and subsequently validated in 115 fish. Sequence analyses revealed a high similarity between the identified sex-specific marker and the 3' UTR of the aminomethyl transferase (amt) gene of the closely related platyfish (Xiphophorus maculatus). This is the first time that RNA-seq has been used to successfully characterize a sex-specific marker in a fish species in the absence of a genome map. Additionally, the identified sex-specific marker represents one of only a handful of such markers in fishes.}, language = {en} } @article{AdolfiHerpinRegensburgeretal.2016, author = {Adolfi, Mateus C. and Herpin, Amaury and Regensburger, Martina and Sacquegno, Jacopo and Waxman, Joshua S. and Schartl, Manfred}, title = {Retinoic acid and meiosis induction in adult versus embryonic gonads of medaka}, series = {Scientific Reports}, volume = {6}, journal = {Scientific Reports}, doi = {10.1038/srep34281}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-147843}, pages = {34281}, year = {2016}, abstract = {In vertebrates, one of the first recognizable sex differences in embryos is the onset of meiosis, known to be regulated by retinoic acid (RA) in mammals. We investigated in medaka a possible meiotic function of RA during the embryonic sex determination (SD) period and in mature gonads. We found RA mediated transcriptional activation in germ cells of both sexes much earlier than the SD stage, however, no such activity during the critical stages of SD. In adults, expression of the RA metabolizing enzymes indicates sexually dimorphic RA levels. In testis, RA acts directly in Sertoli, Leydig and pre-meiotic germ cells. In ovaries, RA transcriptional activity is highest in meiotic oocytes. Our results show that RA plays an important role in meiosis induction and gametogenesis in adult medaka but contrary to common expectations, not for initiating the first meiosis in female germ cells at the SD stage.}, language = {en} } @article{BrunetVolffSchartl2016, author = {Brunet, Fr{\´e}d{\´e}ric G. and Volff, Jean-Nicolas and Schartl, Manfred}, title = {Whole Genome Duplications Shaped the Receptor Tyrosine Kinase Repertoire of Jawed Vertebrates}, series = {Genome Biology Evolution}, volume = {8}, journal = {Genome Biology Evolution}, number = {15}, doi = {10.1093/gbe/evw103}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-146988}, pages = {1600-1613}, year = {2016}, abstract = {The receptor tyrosine kinase (RTK) gene family, involved primarily in cell growth and differentiation, comprises proteins with a common enzymatic tyrosine kinase intracellular domain adjacent to a transmembrane region. The amino-terminal portion of RTKs is extracellular and made of different domains, the combination of which characterizes each of the 20 RTK subfamilies among mammals. We analyzed a total of 7,376 RTK sequences among 143 vertebrate species to provide here the first comprehensive census of the jawed vertebrate repertoire. We ascertained the 58 genes previously described in the human and mouse genomes and established their phylogenetic relationships. We also identified five additional RTKs amounting to a total of 63 genes in jawed vertebrates. We found that the vertebrate RTK gene family has been shaped by the two successive rounds of whole genome duplications (WGD) called 1R and 2R (1R/2R) that occurred at the base of the vertebrates. In addition, the Vegfr and Ephrin receptor subfamilies were expanded by single gene duplications. In teleost fish, 23 additional RTK genes have been retained after another expansion through the fish-specific third round (3R) of WGD. Several lineage-specific gene losses were observed. For instance, birds have lost three RTKs, and different genes are missing in several fish sublineages. The RTK gene family presents an unusual high gene retention rate from the vertebrate WGDs (58.75\% after 1R/2R, 64.4\% after 3R), resulting in an expansion that might be correlated with the evolution of complexity of vertebrate cellular communication and intracellular signaling.}, language = {en} } @article{KneitzMishraChalopinetal.2016, author = {Kneitz, Susanne and Mishra, Rasmi R. and Chalopin, Domitille and Postlethwait, John and Warren, Wesley C. and Walther, Ronald B. and Schartl, Manfred}, title = {Germ cell and tumor associated piRNAs in the medaka and \(Xiphophorus\) melanoma models}, series = {BMC Genomics}, volume = {17}, journal = {BMC Genomics}, number = {357}, doi = {10.1186/s12864-016-2697-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-146028}, year = {2016}, abstract = {Background A growing number of studies report an abnormal expression of Piwi-interacting RNAs (piRNAs) and the piRNA processing enzyme Piwi in many cancers. Whether this finding is an epiphenomenon of the chaotic molecular biology of the fast dividing, neoplastically transformed cells or is functionally relevant to tumorigenesisis is difficult to discern at present. To better understand the role of piRNAs in cancer development small laboratory fish models can make a valuable contribution. However, little is known about piRNAs in somatic and neoplastic tissues of fish. Results To identify piRNA clusters that might be involved in melanoma pathogenesis, we use several transgenic lines of medaka, and platyfish/swordtail hybrids, which develop various types of melanoma. In these tumors Piwi, is expressed at different levels, depending on tumor type. To quantify piRNA levels, whole piRNA populations of testes and melanomas of different histotypes were sequenced. Because no reference piRNA cluster set for medaka or Xiphophorus was yet available we developed a software pipeline to detect piRNA clusters in our samples and clusters were selected that were enriched in one or more samples. We found several loci to be overexpressed or down-regulated in different melanoma subtypes as compared to hyperpigmented skin. Furthermore, cluster analysis revealed a clear distinction between testes, low-grade and high-grade malignant melanoma in medaka. Conclusions Our data imply that dysregulation of piRNA expression may be associated with development of melanoma. Our results also reinforce the importance of fish as a suitable model system to study the role of piRNAs in tumorigenesis.}, language = {en} } @article{SchulSchmittRegnerietal.2013, author = {Schul, Daniela and Schmitt, Alexandra and Regneri, Janine and Schartl, Manfred and Wagner, Toni Ulrich}, title = {Bursted BMP Triggered Receptor Kinase Activity Drives Smad1 Mediated Long-Term Target Gene Oscillation in c2c12 Cells}, series = {PLoS ONE}, volume = {8}, journal = {PLoS ONE}, number = {4}, doi = {10.1371/journal.pone.0059442}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-130131}, pages = {e59442}, year = {2013}, abstract = {Bone Morphogenetic Proteins (BMPs) are important growth factors that regulate many cellular processes. During embryogenesis they act as morphogens and play a critical role during organ development. They influence cell fates via concentration-gradients in the embryos where cells transduce this extracellular information into gene expression profiles and cell fate decisions. How receiving cells decode and quantify BMP2/4 signals is hardly understood. There is little data on the quantitative relationships between signal input, transducing molecules, their states and location, and ultimately their ability to integrate graded systemic inputs and generate qualitative responses. Understanding this signaling network on a quantitative level should be considered a prerequisite for efficient pathway modulation, as the BMP pathway is a prime target for therapeutic invention. Hence, we quantified the spatial distribution of the main signal transducer of the BMP2/4 pathway in response to different types and levels of stimuli in c2c12 cells. We found that the subcellular localization of Smad1 is independent of ligand concentration. In contrast, Smad1 phosphorylation levels relate proportionally to BMP2 ligand concentrations and they are entirely located in the nucleus. Interestingly, we found that BMP2 stimulates target gene expression in non-linear, wave-like forms. Amplitudes showed a clear concentration-dependency, for sustained and transient stimulation. We found that even burst-stimulation triggers gene-expression wave-like modulations that are detectable for at least 30 h. Finally, we show here that target gene expression oscillations depend on receptor kinase activity, as the kinase drives further expression pulses without receptor reactivation and the target gene expression breaks off after inhibitor treatment in c2c12 cells.}, language = {en} } @article{SchartlWalterShenetal.2013, author = {Schartl, Manfred and Walter, Ronald B. and Shen, Yingjia and Garcia, Tzintzuni and Catchen, Julian and Amores, Angel and Braasch, Ingo and Chalopin, Domitille and Volff, Jean-Nicolas and Lesch, Klaus-Peter and Bisazza, Angelo and Minx, Pat and Hillier, LaDeana and Wilson, Richard K. and F{\"u}rstenberg, Susan and Boore, Jeffrey and Searle, Steve and Postlethwait, John H. and Warren, Wesley C.}, title = {The genome of the platyfish, Xiphophorus maculatus, provides insights into evolutionary adaptation and several complex traits}, series = {Nature Genetics}, volume = {45}, journal = {Nature Genetics}, number = {5}, doi = {10.1038/ng.2604}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-132152}, pages = {567-572}, year = {2013}, abstract = {Several attributes intuitively considered to be typical mammalian features, such as complex behavior, live birth and malignant disease such as cancer, also appeared several times independently in lower vertebrates. The genetic mechanisms underlying the evolution of these elaborate traits are poorly understood. The platyfish, X. maculatus, offers a unique model to better understand the molecular biology of such traits. We report here the sequencing of the platyfish genome. Integrating genome assembly with extensive genetic maps identified an unexpected evolutionary stability of chromosomes in fish, in contrast to in mammals. Genes associated with viviparity show signatures of positive selection, identifying new putative functional domains and rare cases of parallel evolution. We also find that genes implicated in cognition show an unexpectedly high rate of duplicate gene retention after the teleost genome duplication event, suggesting a hypothesis for the evolution of the behavioral complexity in fish, which exceeds that found in amphibians and reptiles.}, language = {en} } @article{HerpinAdolfiNicoletal.2013, author = {Herpin, Amaury and Adolfi, Mateus C. and Nicol, Barbara and Hinzmann, Maria and Schmidt, Cornelia and Klughammer, Johanna and Engel, Mareen and Tanaka, Minoru and Guiguen, Yann and Schartl, Manfred}, title = {Divergent Expression Regulation of Gonad Development Genes in Medaka Shows Incomplete Conservation of the Downstream Regulatory Network of Vertebrate Sex Determination}, series = {Molecular Biology and Evolution}, volume = {30}, journal = {Molecular Biology and Evolution}, number = {10}, doi = {10.1093/molbev/mst130}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-132262}, pages = {2328-2346}, year = {2013}, abstract = {Genetic control of male or female gonad development displays between different groups of organisms a remarkable diversity of "master sex-determining genes" at the top of the genetic hierarchies, whereas downstream components surprisingly appear to be evolutionarily more conserved. Without much further studies, conservation of sequence has been equalized to conservation of function. We have used the medaka fish to investigate the generality of this paradigm. In medaka, the master male sex-determining gene is dmrt1bY, a highly conserved downstream regulator of sex determination in vertebrates. To understand its function in orchestrating the complex gene regulatory network, we have identified targets genes and regulated pathways of Dmrt1bY. Monitoring gene expression and interactions by transgenic fluorescent reporter fish lines, in vivo tissue-chromatin immunoprecipitation and in vitro gene regulation assays revealed concordance but also major discrepancies between mammals and medaka, notably amongst spatial, temporal expression patterns and regulations of the canonical Hedgehog and R-spondin/Wnt/Follistatin signaling pathways. Examination of Foxl2 protein distribution in the medaka ovary defined a new subpopulation of theca cells, where ovarian-type aromatase transcriptional regulation appears to be independent of Foxl2. In summary, these data show that the regulation of the downstream regulatory network of sex determination is less conserved than previously thought.}, language = {en} } @article{YanHongChenetal.2013, author = {Yan, Yan and Hong, Ni and Chen, Tiansheng and Li, Mingyou and Wang, Tiansu and Guan, Guijun and Qiao, Yongkang and Chen, Songlin and Schartl, Manfred and Li, Chang-Ming and Hong, Yunhan}, title = {p53 Gene Targeting by Homologous Recombination in Fish ES Cells}, series = {PLoS One}, volume = {8}, journal = {PLoS One}, number = {3}, doi = {10.1371/journal.pone.0059400}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-133416}, pages = {e59400}, year = {2013}, abstract = {Background: Gene targeting (GT) provides a powerful tool for the generation of precise genetic alterations in embryonic stem (ES) cells to elucidate gene function and create animal models for human diseases. This technology has, however, been limited to mouse and rat. We have previously established ES cell lines and procedures for gene transfer and selection for homologous recombination (HR) events in the fish medaka (Oryzias latipes). Methodology and Principal Findings: Here we report HR-mediated GT in this organism. We designed a GT vector to disrupt the tumor suppressor gene p53 (also known as tp53). We show that all the three medaka ES cell lines, MES1 similar to MES3, are highly proficient for HR, as they produced detectable HR without drug selection. Furthermore, the positive-negative selection (PNS) procedure enhanced HR by similar to 12 folds. Out of 39 PNS-resistant colonies analyzed, 19 (48.7\%) were positive for GT by PCR genotyping. When 11 of the PCR-positive colonies were further analyzed, 6 (54.5\%) were found to be bona fide homologous recombinants by Southern blot analysis, sequencing and fluorescent in situ hybridization. This produces a high efficiency of up to 26.6\% for p53 GT under PNS conditions. We show that p53 disruption and long-term propagation under drug selection conditions do not compromise the pluripotency, as p53-targeted ES cells retained stable growth, undifferentiated phenotype, pluripotency gene expression profile and differentiation potential in vitro and in vivo. Conclusions: Our results demonstrate that medaka ES cells are proficient for HR-mediated GT, offering a first model organism of lower vertebrates towards the development of full ES cell-based GT technology.}, language = {en} } @article{ForconiCanapaBaruccaetal.2013, author = {Forconi, Mariko and Canapa, Adriana and Barucca, Marco and Biscotti, Maria A. and Capriglione, Teresa and Buonocore, Francesco and Fausto, Anna M. and Makapedua, Daisy M. and Pallavicini, Alberto and Gerdol, Marco and De Moro, Gianluca and Scapigliati, Giuseppe and Olmo, Ettore and Schartl, Manfred}, title = {Characterization of Sex Determination and Sex Differentiation Genes in Latimeria}, series = {PLoS ONE}, volume = {8}, journal = {PLoS ONE}, number = {4}, doi = {10.1371/journal.pone.0056006}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-130995}, pages = {e56006}, year = {2013}, abstract = {Genes involved in sex determination and differentiation have been identified in mice, humans, chickens, reptiles, amphibians and teleost fishes. However, little is known of their functional conservation, and it is unclear whether there is a common set of genes shared by all vertebrates. Coelacanths, basal Sarcopterygians and unique "living fossils", could help establish an inventory of the ancestral genes involved in these important developmental processes and provide insights into their components. In this study 33 genes from the genome of Latimeria chalumnae and from the liver and testis transcriptomes of Latimeria menadoensis, implicated in sex determination and differentiation, were identified and characterized and their expression levels measured. Interesting findings were obtained for GSDF, previously identified only in teleosts and now characterized for the first time in the sarcopterygian lineage; FGF9, which is not found in teleosts; and DMRT1, whose expression in adult gonads has recently been related to maintenance of sexual identity. The gene repertoire and testis-specific gene expression documented in coelacanths demonstrate a greater similarity to modern fishes and point to unexpected changes in the gene regulatory network governing sexual development.}, language = {en} } @article{KangSchartlWalteretal.2013, author = {Kang, Ji Hyoun and Schartl, Manfred and Walter, Ronald B. and Meyer, Axel}, title = {Comprehensive phylogenetic analysis of all species of swordtails and platies (Pisces: Genus Xiphophorus) uncovers a hybrid origin of a swordtail fish, Xiphophorus monticolus, and demonstrates that the sexually selected sword originated in the ancestral lineage of the genus, but was lost again secondarily}, series = {BMC Evolutionary Biology}, volume = {13}, journal = {BMC Evolutionary Biology}, number = {25}, issn = {1471-2148}, doi = {10.1186/1471-2148-13-25}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-121853}, year = {2013}, abstract = {Background: Males in some species of the genus Xiphophorus, small freshwater fishes from Meso-America, have an extended caudal fin, or sword - hence their common name "swordtails". Longer swords are preferred by females from both sworded and - surprisingly also, non-sworded (platyfish) species that belong to the same genus. Swordtails have been studied widely as models in research on sexual selection. Specifically, the pre-existing bias hypothesis was interpreted to best explain the observed bias of females in presumed ancestral lineages of swordless species that show a preference for assumed derived males with swords over their conspecific swordless males. However, many of the phylogenetic relationships within this genus still remained unresolved. Here we construct a comprehensive molecular phylogeny of all 26 known Xiphophorus species, including the four recently described species (X. kallmani, X. mayae, X. mixei and X. monticolus). We use two mitochondrial and six new nuclear markers in an effort to increase the understanding of the evolutionary relationships among the species in this genus. Based on the phylogeny, the evolutionary history and character state evolution of the sword was reconstructed and found to have originated in the common ancestral lineage of the genus Xiphophorus and that it was lost again secondarily. Results: We estimated the evolutionary relationships among all known species of the genus Xiphophorus based on the largest set of DNA markers so far. The phylogeny indicates that one of the newly described swordtail species, Xiphophorus monticolus, is likely to have arisen through hybridization since it is placed with the southern platyfish in the mitochondrial phylogeny, but with the southern swordtails in the nuclear phylogeny. Such discordance between these two types of markers is a strong indication for a hybrid origin. Additionally, by using a maximum likelihood approach the possession of the sexually selected sword trait is shown to be the most likely ancestral state for the genus Xiphophorus. Further, we provide a well supported estimation of the phylogenetic relationships between the previously unresolved northern swordtail groups. Conclusions: This comprehensive molecular phylogeny of the entire genus Xiphophorus provides evidence that a second swordtail species, X. monticolus, arose through hybridization. Previously, we demonstrated that X. clemenciae, another southern swordtail species, arose via hybridization. These findings highlight the potential key role of hybridization in the evolution of this genus and suggest the need for further investigations into how hybridization contributes to speciation more generally.}, language = {en} } @article{HaydnHufnagelGrimmetal.2014, author = {Haydn, Johannes M. and Hufnagel, Anita and Grimm, Johannes and Maurus, Katja and Schartl, Manfred and Meierjohann, Svenja}, title = {The MAPK pathway as an apoptosis enhancer in melanoma}, series = {Oncotarget}, volume = {5}, journal = {Oncotarget}, number = {13}, issn = {1949-2553}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-120649}, pages = {5040-53}, year = {2014}, abstract = {Inhibition of RAF/MEK/ERK signaling is beneficial for many patients with BRAFV600E-mutated melanoma. However, primary and secondary resistances restrict long-lasting therapy success. Combination therapies are therefore urgently needed. Here, we evaluate the cellular effect of combining a MEK inhibitor with a genotoxic apoptosis inducer. Strikingly, we observed that an activated MAPK pathway promotes in several melanoma cell lines the pro-apoptotic response to genotoxic stress, and MEK inhibition reduces intrinsic apoptosis. This goes along with MEK inhibitor induced increased RAS and P-AKT levels. The protective effect of the MEK inhibitor depends on PI3K signaling, which prevents the induction of pro-apoptotic PUMA that mediates apoptosis after DNA damage. We could show that the MEK inhibitor dependent feedback loop is enabled by several factors, including EGF receptor and members of the SPRED family. The simultaneous knockdown of SPRED1 and SPRED2 mimicked the effects of MEK inhibitor such as PUMA repression and protection from apoptosis. Our data demonstrate that MEK inhibition of BRAFV600E-positive melanoma cells can protect from genotoxic stress, thereby achieving the opposite of the intended anti-tumorigenic effect of the combination of MEK inhibitor with inducers of intrinsic apoptosis.}, language = {en} } @article{AdolfiCarreiraJesusetal.2015, author = {Adolfi, Mateus C. and Carreira, Ana C. O. and Jesus, L{\´a}zaro W. O. and Bogerd, Jan and Funes, Rejane M. and Schartl, Manfred and Sogayar, Mari C. and Borella, Maria I.}, title = {Molecular cloning and expression analysis of dmrt1 and sox9 during gonad development and male reproductive cycle in the lambari fish, Astyanax altiparanae}, series = {Reproductive Biology and Endocrinology}, volume = {13}, journal = {Reproductive Biology and Endocrinology}, number = {2}, doi = {10.1186/1477-7827-13-2}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-126486}, year = {2015}, abstract = {Background The dmrt1 and sox9 genes have a well conserved function related to testis formation in vertebrates, and the group of fish presents a great diversity of species and reproductive mechanisms. The lambari fish (Astyanax altiparanae) is an important Neotropical species, where studies on molecular level of sex determination and gonad maturation are scarce. Methods Here, we employed molecular cloning techniques to analyze the cDNA sequences of the dmrt1 and sox9 genes, and describe the expression pattern of those genes during development and the male reproductive cycle by qRT-PCR, and related to histology of the gonad. Results Phylogenetic analyses of predicted amino acid sequences of dmrt1 and sox9 clustered A. altiparanae in the Ostariophysi group, which is consistent with the morphological phylogeny of this species. Studies of the gonad development revealed that ovary formation occurred at 58 days after hatching (dah), 2 weeks earlier than testis formation. Expression studies of sox9 and dmrt1 in different tissues of adult males and females and during development revealed specific expression in the testis, indicating that both genes also have a male-specific role in the adult. During the period of gonad sex differentiation, dmrt1 seems to have a more significant role than sox9. During the male reproductive cycle dmrt1 and sox9 are down-regulated after spermiation, indicating a role of these genes in spermatogenesis. Conclusions For the first time the dmrt1 and sox9 were cloned in a Characiformes species. We show that both genes have a conserved structure and expression, evidencing their role in sex determination, sex differentiation and the male reproductive cycle in A. altiparanae. These findings contribute to a better understanding of the molecular mechanisms of sex determination and differentiation in fish.}, language = {en} } @article{Schartl2014, author = {Schartl, Manfred}, title = {Beyond the zebrafish: diverse fish species for modeling human disease}, series = {Disease Models \& Mechanisms}, volume = {7}, journal = {Disease Models \& Mechanisms}, number = {2}, issn = {1754-8411}, doi = {10.1242/dmm.012245}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-119919}, year = {2014}, abstract = {In recent years, zebrafish, and to a lesser extent medaka, have become widely used small animal models for human diseases. These organisms have convincingly demonstrated the usefulness of fish for improving our understanding of the molecular and cellular mechanisms leading to pathological conditions, and for the development of new diagnostic and therapeutic tools. Despite the usefulness of zebrafish and medaka in the investigation of a wide spectrum of traits, there is evidence to suggest that other fish species could be better suited for more targeted questions. With the emergence of new, improved sequencing technologies that enable genomic resources to be generated with increasing efficiency and speed, the potential of non-mainstream fish species as disease models can now be explored. A key feature of these fish species is that the pathological condition that they model is often related to specific evolutionary adaptations. By exploring these adaptations, new disease-causing and disease-modifier genes might be identified; thus, diverse fish species could be exploited to better understand the complexity of disease processes. In addition, non-mainstream fish models could allow us to study the impact of environmental factors, as well as genetic variation, on complex disease phenotypes. This Review will discuss the opportunities that such fish models offer for current and future biomedical research.}, language = {en} } @article{TomaszkiewiczChalopinSchartletal.2014, author = {Tomaszkiewicz, Marta and Chalopin, Domitille and Schartl, Manfred and Galiana, Delphine and Volff, Jean-Nicolas}, title = {A multicopy Y-chromosomal SGNH hydrolase gene expressed in the testis of the platyfish has been captured and mobilized by a Helitron transposon}, series = {BMC Genetics}, volume = {15}, journal = {BMC Genetics}, number = {44}, doi = {10.1186/1471-2156-15-44}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-116746}, year = {2014}, abstract = {Background: Teleost fish present a high diversity of sex determination systems, with possible frequent evolutionary turnover of sex chromosomes and sex-determining genes. In order to identify genes involved in male sex determination and differentiation in the platyfish Xiphophorus maculatus, bacterial artificial chromosome contigs from the sex-determining region differentiating the Y from the X chromosome have been assembled and analyzed. Results: A novel three-copy gene called teximY (for testis-expressed in Xiphophorus maculatus on the Y) was identified on the Y but not on the X chromosome. A highly related sequence called texim1, probably at the origin of the Y-linked genes, as well as three more divergent texim genes were detected in (pseudo) autosomal regions of the platyfish genome. Texim genes, for which no functional data are available so far in any organism, encode predicted esterases/lipases with a SGNH hydrolase domain. Texim proteins are related to proteins from very different origins, including proteins encoded by animal CR1 retrotransposons, animal platelet-activating factor acetylhydrolases (PAFah) and bacterial hydrolases. Texim gene distribution is patchy in animals. Texim sequences were detected in several fish species including killifish, medaka, pufferfish, sea bass, cod and gar, but not in zebrafish. Texim-like genes are also present in Oikopleura (urochordate), Amphioxus (cephalochordate) and sea urchin (echinoderm) but absent from mammals and other tetrapods. Interestingly, texim genes are associated with a Helitron transposon in different fish species but not in urochordates, cephalochordates and echinoderms, suggesting capture and mobilization of an ancestral texim gene in the bony fish lineage. RT-qPCR analyses showed that Y-linked teximY genes are preferentially expressed in testis, with expression at late stages of spermatogenesis (late spermatids and spermatozeugmata). Conclusions: These observations suggest either that TeximY proteins play a role in Helitron transposition in the male germ line in fish, or that texim genes are spermatogenesis genes mobilized and spread by transposable elements in fish genomes.}, language = {en} } @article{GarciaMatosShenetal.2014, author = {Garcia, Tzintzuni I. and Matos, Isa and Shen, Yingjia and Pabuwal, Vagmita and Coelho, Maria Manuela and Wakamatsu, Yuko and Schartl, Manfred and Walter, Ronald B.}, title = {Novel Method for Analysis of Allele Specific Expression in Triploid Oryzias latipes Reveals Consistent Pattern of Allele Exclusion}, series = {PLOS ONE}, volume = {9}, journal = {PLOS ONE}, number = {6}, issn = {1932-6203}, doi = {10.1371/journal.pone.0100250}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-116000}, pages = {e100250}, year = {2014}, abstract = {Assessing allele-specific gene expression (ASE) on a large scale continues to be a technically challenging problem. Certain biological phenomena, such as X chromosome inactivation and parental imprinting, affect ASE most drastically by completely shutting down the expression of a whole set of alleles. Other more subtle effects on ASE are likely to be much more complex and dependent on the genetic environment and are perhaps more important to understand since they may be responsible for a significant amount of biological diversity. Tools to assess ASE in a diploid biological system are becoming more reliable. Non-diploid systems are, however, not uncommon. In humans full or partial polyploid states are regularly found in both healthy (meiotic cells, polynucleated cell types) and diseased tissues (trisomies, non-disjunction events, cancerous tissues). In this work we have studied ASE in the medaka fish model system. We have developed a method for determining ASE in polyploid organisms from RNAseq data and we have implemented this method in a software tool set. As a biological model system we have used nuclear transplantation to experimentally produce artificial triploid medaka composed of three different haplomes. We measured ASE in RNA isolated from the livers of two adult, triploid medaka fish that showed a high degree of similarity. The majority of genes examined (82\%) shared expression more or less evenly among the three alleles in both triploids. The rest of the genes (18\%) displayed a wide range of ASE levels. Interestingly the majority of genes (78\%) displayed generally consistent ASE levels in both triploid individuals. A large contingent of these genes had the same allele entirely suppressed in both triploids. When viewed in a chromosomal context, it is revealed that these genes are from large sections of 4 chromosomes and may be indicative of some broad scale suppression of gene expression.}, language = {en} } @article{AdamMauelerSchartl1991, author = {Adam, Dieter and Maueler, Winfried and Schartl, Manfred}, title = {Transcriptional activation of the melanoma inducing Xmrk oncogene in Xiphophorus}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-87584}, year = {1991}, abstract = {The melanoma inducing locus of Xiphophorus encodes a tumorigenic version of a novel putative receptor tyrosine kinase (Xmrk). To elucidate the mechanism of oncogenic activation of Xmrk, we compared the structure and expression of two oncogenic loci with the corresponding proto-oncogene. Only minor structural alterations were found to be specific for the oncogenic Xmrk genes. Marked overexpression of the oncogene transcripts in melanoma, which are approximately 1 kb shorter than the proto-oncogene transcript, correlates with the malignancy of the tumors. The tumor transcripts are derived from an alternative transcription start site that is used only in the oncogenic loci. Thus, oncogenic activation of the melanoma inducing Xmrk gene appears primarily to be due to novel transcriptional control and overexpression.}, subject = {Schwertk{\"a}rpfling}, language = {en} } @article{SchartlWittbrodtMaeueleretal.1993, author = {Schartl, Manfred and Wittbrodt, J. and M{\"a}ueler, W. and Raulf, F. and Adam, D. and Hannig, G. and Telling, A. and Storch, F. and Andexinger, S. and Robertson, S. M.}, title = {Oncogenes and melanoma formation in Xiphoporus (Teleostei: Poeciliidae)}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-87149}, year = {1993}, abstract = {In Xiphophorus melanoma formation has been attributed by classical genetic findings to the overexpression of a cellular oncogene (Tu) due to elimination of the corresponding regulatory gene locus in hybrids. We have attempted to elucidate this phenomenon on the molecular biological level. Studies on the structure and expression of known proto-oncogenes revealed that several of these genes, especially the c-src gene of Xiphophorus, may act as effectors in establishing the neoplastic phenotype of the melanoma cells . However, these genes appear more to participate in secondary steps of tumorigenesis. Another gene, being termed Xmrk, which represents obviously a so far unknown proto-oncogene but with a cons iderably high similarity to the epidermal growth-factorreceptor gene, was mapped to the Tu-containing region of the chromosome. This gene shows features with respect to its structure and expression that seem to justify it to be regarded as a candidate for a gene involved in the primary processes leading to neoplastic transformation of pigment cells in Xiphophorus.}, subject = {Schwertk{\"a}rpfling}, language = {en} } @incollection{SchartlErbeldingDenkHoelteretal.1993, author = {Schartl, Manfred and Erbelding-Denk, C. and H{\"o}lter, S. and Nanda, I. and Schmid, M. and Schr{\"o}der, J. H. and Epplen, J. T.}, title = {High mating success of low rank males in Limia perugiae (Pisces: Poeciliidae) as determined by DNA-fingerprinting}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-87132}, publisher = {Universit{\"a}t W{\"u}rzburg}, year = {1993}, abstract = {Hierarchical structures among male individuals in a population are frequently reflected in differences in aggressive and reproductive behaviour and access to the females. In general social dominance requires large investments which in turn may have to be compensated for by high reproductive success. However, this hypothesis has so far only been sufficiently tested in small mating groups due to the difficulties of determining paternity by classical methods using non-molecular markers. DNA fingerprinting overcomes these problems offering the possibility to determine genetic relationships and mating patterns within larger groups. Using this approach we have recently shown (Schartl et al., 1993) that in the poeciliid fish Limia perugiae in small mating groups the dominant male has 100\% mating success, while in larger groups its contribution to the offspring unexpectedly drops to zero. The reproductive failure under such social conditions is explained by the inability of the ex-male to protect all the females simultaneously against mating attempts of his numerous subordinate competitors.}, subject = {DNS}, language = {en} } @article{MeyerSchartl1979, author = {Meyer, Manfred K. and Schartl, Manfred}, title = {Eine neue Xiphophorus-Art aus Vera Cruz, Mexiko : (Pisces: Poeciliidae)}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-87124}, year = {1979}, abstract = {Xiphophorus andersi n. sp. from the Rio Atoyac, Vera Cruz, Mexico is described: lang head, moderately slender body, large dark black spar at the basis of the anal fin; adult male with short sword-like caudal appendage; rip of ray 5a of gonopodium without a developed claw. Xiphophorus andersi n. sp. differs by the combination of distinct characters from all the other species of the genus known so far. The new species shows features of both the so-called platyfish species group and the so-called swordtail species group.}, subject = {Schwertk{\"a}rpfling}, language = {en} } @article{SchartlSchroeder1987, author = {Schartl, Manfred and Schr{\"o}der, Johannes Horst}, title = {A new species of the genus Xiphophorus Heckel 1848, endemic to northern Coahuila, Mexico (Pisces: Poeciliidae)}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-87117}, year = {1987}, abstract = {Xiphophorus meyeri n. sp. is described as an endemic to Muzquiz, Coahuila, Mexico. It appears to be the northernmost species of the genus. The new species is related to X. couchianus and X. gordoni, but differs morphologically from those by dorsal fin ray number, by the expression of some gonopodial features and most markedly by the appearance of macromelanophores or tr-melanophores.}, subject = {Schwertkr{\"a}pfling}, language = {en} } @article{WinklerWittbrodtLammersetal.1994, author = {Winkler, Christoph and Wittbrodt, Joachim and Lammers, Reiner and Ullrich, Axel and Schartl, Manfred}, title = {Ligand-dependent tumor induction in medakafish embryos by a Xmrk receptor tyrosine kinase transgene}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-87107}, year = {1994}, abstract = {Xmrk encodes a subclass 1 receptor tyrosine kinase (RTK) which has been cloned from the melanomainducing locus Tu of the poeciliid fish Xiphophorus. To demonstrate a high oncogenic potential in vivo we transferred the gene into early embryos of the closely related medakafish. Ectopic expression of the Xmrk oncogene under the control of a strong, constitutive promoter (CMVTk) led to the induction of embryonic tumors with high incidence, after short latency periods, and with a specific pattern of affected tissues. We demonstrate ligand-dependent transformation in vivo using a chimeric receptor consisting of the extracellular and transmembrane domains of the human EGF receptor (HER) and the cytoplasmatic domain of Xmrk. Expression of the chimeric receptor alone does not lead to ldnase activation or induction of tumors. Coexpression of the chimera with its corresponding ligand, human transforming growth factor alpha (bTGF(X), however, results in the activation of the chimeric RTK. In injected fish embryos the induction of the neoplastic growth is observed with similar incidence and tissue distribution as in embryos carrying the native Xmrk oncogene suggesting that the ligand as well as factors downstream of tbe RTK are required for tumor formation. In this study we show single-step induction of tumors by ectopic expression of RTKs in vivo substantiating tbe significance of autocrine stimulation in RTK induced tumors in vertebrales.}, subject = {Japank{\"a}rpfling}, language = {en} } @article{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} } @inproceedings{SchreibmanSchartlKallmanetal.1994, author = {Schreibman, Martin P. and Schartl, Manfred and Kallman, Klaus D. and Magliulo-Cepriano, Lucia}, title = {Molecular approaches to study the genetic regulation of the fish reproductive system}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-86679}, year = {1994}, abstract = {No abstract available.}, subject = {Fische}, language = {en} } @inproceedings{SchartlSchartlAnders1981, author = {Schartl, A. and Schartl, Manfred and Anders, F.}, title = {Phenotypic conversion of malignant melanoma to benign melanoma and vice versa in Xiphophorus}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-86662}, year = {1981}, abstract = {No abstract available.}, subject = {Schwertk{\"a}rpfling}, language = {en} } @inproceedings{AndersSchollSchartl1981, author = {Anders, F. and Scholl, E. and Schartl, Manfred}, title = {Environmental and hereditary factors in the causation of neoplasia, based on studies of the Xiphophorus fish melanoma system}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-86402}, year = {1981}, abstract = {Neoplasia in Xiphophorus can be classified into: a) a Jarge group triggered by carcinogens; b) a large group triggered by promoters; and c) a small group that develops "spontaneously" according to Mendelian Jaw. The process leading to susceptibility for neoplasia is represented by the disintegration of gene systems that normally protect the fish from neoplasia. Interpopulational arid interracial hybridization is the most effective process that Ieads to disintegration of the protective gene systems. Environmental factors may complete disintegration in somatic cells and thus may trigger neoplasia. The applications of the findings on Xiphophorus to humans are discussed.}, subject = {Schwertk{\"a}rpfling}, language = {en} } @inproceedings{AndersSchartlBarnekow1984, author = {Anders, Fritz and Schartl, Manfred and Barnekow, Angelika}, title = {Xiphophorus as an in vivo model for studies on oncogenes}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-86398}, year = {1984}, abstract = {The capacity of Xiphophorus to develop neoplasia can be formally assigned to a "tumor gene" (Tu), which appears to be a normal part of the genome of all individuals. The wild fish have evolved population-specific and cell type-specific systems of regulatory genes (R) for Tu that protect the fish from neoplasia. Hybridization of members of different wild populations in the laborstory followed by treatment of the hybrids with carcinogens led to disintegration of the R systems permitting excessive expression of Tu and thus resulting in neoplasia. Certain hybrids developed neoplasia even spontaneously. Observations on the genuine phenotypic effect of the derepressed Tu in the early embryo indicated an essential normal function of this oncogene in cell differentiation, proliferation and cell-cell communication. Tu appeared to be indispensable in the genome but may also be present in accessory copics. Recently, c-src, the cellular homolog of the Rous sarcoma virus oncogene v-src, was detected in Xiphophorus. The protein product of c-src, pp60c-src, was identified and then examined by its associated kinase activity. This pp60c-src was found in all individuals tested, but, depending on the genotype, its kinase activity was different. The genetic characters of c-src, such as linkage relations, dosage relations, expression, etc., correspond to those of Tu. From a systematic study which showed that pp60c-src was present in all metazoa tested ranging from mammals down to sponges, we concluded that c-src has evolved with the multicellular organization of animals. Neoplasia of animals and humans is a characteristic closely related to this evolution. Our data showed that small aquariurn fish, besides being used successfully because they are time-, space-, and money-saving systems for carcinogenicity testing, are also highly suitable for basic studies on neoplasia at the populational, morphological, developmental, cell biological, and molecular levels.}, subject = {Schwertk{\"a}rpfling}, language = {en} } @incollection{AdamSchartlAndexingeretal.1991, author = {Adam, D. and Schartl, A. and Andexinger, S. and H{\"o}lter, S. and Wilde, B. and Schartl, Manfred}, title = {Genetic factors in tumour formation: The melanoma-inducing gene of Xiphophorus}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-86388}, publisher = {Universit{\"a}t W{\"u}rzburg}, year = {1991}, abstract = {No abstract available.}, subject = {Humangenetik}, language = {en} } @incollection{EpplenAmmerEpplenetal.1991, author = {Epplen, J. T. and Ammer, H. and Epplen, C. and Kammerbauer, C. and Mitreiter, R. and Roewer, L. and Schwaiger, W. and Steimle, V. and Zischler, H. and Albert, E. and Andreas, A. and Beyermann, B. and Meyer, W. and Buitkamp, J. and Nanda, I. and N{\"u}rnberg, P. and Pena, S. D. J. and P{\"o}che, H. and Sprecher, W. and Schartl, Manfred and Weising, K. and Yassouridis, A.}, title = {Oligonucleotide fingerprinting using simple repeat motifs: a convenient, ubiquitously applicable method to detect hypervariability for multiple purposes}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-86371}, publisher = {Universit{\"a}t W{\"u}rzburg}, year = {1991}, abstract = {A panel of simple repetitive oligonucleotide probes has been designed and tested for multilocus DNA fingerprinting in some 200 fungal, plant and animal species as well as man. To date at least one of the probes has been found to be informative in each species. The human genome, however, has been the major target of many fingerprintins studies. Using the probe (CAC)5 or (GTG)5, individualization of all humans is possible except for monozygotic twins. Paternity analyses are now perfonned on a routine basis by the use of multilocus fingerprints, inctuding also cases of deficiency, i.e. where one of the parents is not available for analysis. In forensie science stain analysis is feasible in all tissue remains containing nuc)eated cells. Depending on the degree of DNA degradation a variety of oligonucleotides are informative, and they have been proven useful in actual case work. Advantages in comparison to other methods including enzymatic DNA amplification techniques (PCR) are evident. Fingerprint patterns of tumors may be changed due to the gain or loss of chromosomes and/or intrachromosomal deletion and amplification events. Locus-specific probes were isolated from the human (CAC)5/( GTG)5 fingerprint with a varying degree of informativeness (monomorphic versus truly hypervariable markers). The feasibility of three different approaches. for the isolation of hypervariable mono-locus probes was evaluated. Finally, one particular mixed simple (gt)n(ga)m repeat locus in the second intron of the HLA-DRB genes has been scrutinized to allow comparison of the extent of exon-encoded (protein-) polymorphisms versus intronie bypervariability of simple repeats: adjacent to a single gene sequence (e.g. HLA-DRB1*0401) many different length alleles were found. Group-specific structures of basic repeats were identified within the evolutionarily related DRB alleles. As a further application it is suggested here that due to the ubiquitous interspersion of their targets, short probes for simple repeat sequences are especially useful tools for ordering genomic cosmid, yeast artificial chromosome and phage banks.}, subject = {DNS}, language = {en} } @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} } @incollection{AltschmiedSchartl1994, author = {Altschmied, Joachim and Schartl, Manfred}, title = {Genetics and molecular biology of tumour formation in Xiphophorus}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-69752}, publisher = {Universit{\"a}t W{\"u}rzburg}, year = {1994}, abstract = {No abstract available.}, subject = {Schwertk{\"a}rpfling}, language = {en} } @inproceedings{PeterSchartlAndersetal.1985, author = {Peter, R. U. and Schartl, Manfred and Anders, F. and Duncker, H.-R.}, title = {Pigment pattern formation during embryogenesis in Xiphophorus}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-69370}, year = {1985}, abstract = {No abstract available.}, subject = {Schwertk{\"a}rpfling}, language = {en} } @inproceedings{RiehlSchartlAnders1985, author = {Riehl, R{\"u}diger and Schartl, Manfred and Anders, Fritz}, title = {An ultrastructural study of melanoma in Xiphophorus}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-70978}, year = {1985}, abstract = {Melanotic melanoma (MM) of Xiphophorus (Teleostei: Poeciliidae) was studied by conventional preparations and freeze-etch preparations for electron microscopy. MM of Xiphophorus exhibits tightly packed pigment cells with prominent dendritic processes and interdigitations of their plasma membranes. The most impressive feature of MM cells is the occurrence of Iarge lobulated nuclei with numerous nuclear pores and some nuclear pockets. Abundant spheroidal or ellipsoidal melanosomes (diameter 200-650 nm) and vesicular structures are distributed throughout the cellular dendrites, whereas the perinucJear cytoplasm is free of melanosomes. A further characteristic feature of melanoma cells in fish is the occurrence of melanosome complexes (i.e., "compound melanosomes"). These melanosome complexes consist of a few to numerous melanosomes, which are enveloped by a separate rnembrane. Pinocytotic vesicles couJd be demonstrated with distinct differences in frequency and distribution patterns, indicating differences in the metabolic activities of the cells in the same melanoma. Intercellular junctions are lacking in the MM cells. The conventional TEM technique showed clear advantages in the demonstration of intemal architecture of organelles, whereas FE bad considerable potential in respect to the visualization of membrane surface specializations.}, subject = {Schwertk{\"a}rpfling}, language = {en} } @inproceedings{SchartlMaeuelerRaulfetal.1988, author = {Schartl, Manfred and M{\"a}ueler, Winfried and Raulf, Friedrich and Robertson, Scott M.}, title = {Molecular aspects of melanoma formation in Xiphophorus}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-72689}, year = {1988}, abstract = {No abstract available.}, subject = {Schwertk{\"a}rpfling}, language = {en} } @article{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} } @inproceedings{AndersSchartlScholl1981, author = {Anders, F. and Schartl, Manfred and Scholl, E.}, title = {Evaluation of environmental and hereditary factors in carcinogenesis, based on studies in Xiphophorus}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-72741}, year = {1981}, abstract = {Neoplasia in Xiphophorus can be classified into a) a large group that is triggered by carcinogens; b) a large group triggered by promoters; c) a small group that develops "spontaneously" following interpopulational and interracial hybridizations; and d) a small group that develops "spontaneously" following germ line mutation. The process leading to susceptibility for neoplasia is represented by the disintegration of gene systems that normally protect the fish from neoplasia. Hybridization is the most effective process that leads to disintegration of the protection gene systems. Environmental factors may complete disintegration and thus may trigger neoplasia. It is discussed whether the findings on Xiphophorus may also apply to humans.}, subject = {Schwertk{\"a}rpfling}, language = {en} } @incollection{AndersSchollSchartl1979, author = {Anders, F. and Scholl, E. and Schartl, Manfred}, title = {Xiphophorus als Modell in der Krebsforschung}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-72752}, publisher = {Universit{\"a}t W{\"u}rzburg}, year = {1979}, abstract = {No abstract available.}, subject = {Schwertk{\"a}rpfling}, language = {de} } @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} }