@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}
}