<> "The repository administrator has not yet configured an RDF license."^^ . <> . . "Egfr-signaling in Oryzias latipes - Characterization of inducible oncogene gain-of-function and receptor loss-of-function Medaka lines"^^ . "One of the major growth-promoting factors in animal development and growth is the epidermal growth factor receptor (Egfr). The Egfr pathway is involved in proliferation, cell survival, migration and differentiation and is one of the most commonly deregulated pathways in cancer. Medaka fish have two copies of the egfr gene, egfr a and b, which have so far not been analyzed for their particular function and redundancy. \r\nTo understand the role of Egfr signaling in the neural stem cell zones of the retina and the brain, we performed a whole mount in situ hybridization screen for egfrs, selected ligands as well as selected downstream signal transducers. We found that both egfrs are broadly and overlapping expressed during development and more specifically in proliferative zones of the brain and the ciliary marginal zone in hatchlings.\r\nTo determine the effect of enhanced growth signaling on the retinal stem and progenitor cells we created a versatile toolbox for targeted induction of Egfr-related oncogenes (Xmrk, myrAKT, and K-Ras12V) in cell types of interest. To this end, we tagged the Egfr variant Xmrk with a fluorescent protein and demonstrated its oncogenicity in a somitic overproliferation assay. A Cre-loxP based induction of oncogenes in single cells in somites and also in the retina was successfully achieved in transient and stable lines, and multiple lines were generated. The analysis of oncogenic effects on RSCs was however hampered by the loss of visible expression in later generations in the retina and brain. \r\nTo analyze the specific role of Egfra in development and growth I generated a CRISPR/Cas9 based knockout (KO) disrupting the open reading frame by GFP-plasmid insertion or deletion and analyzed the resulting phenotype. Egfra-KO fish develop and reproduce normally but have a defect in oogenesis. Oocytes derived from homozygous Egfra-KO females contain multiple sperm entry sites (micropyles), which causes polyspermy and therefore lethality. The characterization of the polyspermy phenotype, as well as the oogenesis defect in adult ovaries, points towards a role of Egfra in the communication between the granulosa cell layer and the oocyte to specify the micropyle.\r\nBy generation of genetic loss and gain of function tools for Egfra and related oncogenes, this work will contribute to understanding the general and the more specific role of Egfr signaling in growth and development of the Medaka fish."^^ . "2017" . . . . . . . "Eva Mareike"^^ . "Hasel"^^ . "Eva Mareike Hasel"^^ . . . . . . "Egfr-signaling in Oryzias latipes - Characterization of inducible oncogene gain-of-function and receptor loss-of-function Medaka lines (Other)"^^ . . . . . . "lightbox.jpg"^^ . . . "Egfr-signaling in Oryzias latipes - Characterization of inducible oncogene gain-of-function and receptor loss-of-function Medaka lines (Other)"^^ . . . . . . "preview.jpg"^^ . . . "Egfr-signaling in Oryzias latipes - Characterization of inducible oncogene gain-of-function and receptor loss-of-function Medaka lines (Other)"^^ . . . . . . "medium.jpg"^^ . . . "Egfr-signaling in Oryzias latipes - Characterization of inducible oncogene gain-of-function and receptor loss-of-function Medaka lines (Other)"^^ . . . . . . "small.jpg"^^ . . . "Egfr-signaling in Oryzias latipes - Characterization of inducible oncogene gain-of-function and receptor loss-of-function Medaka lines (Other)"^^ . . . . . . "indexcodes.txt"^^ . . . "Egfr-signaling in Oryzias latipes - Characterization of inducible oncogene gain-of-function and receptor loss-of-function Medaka lines (PDF)"^^ . . . "170321_Dissertation_EvaHasel_final.pdf"^^ . . "HTML Summary of #23011 \n\nEgfr-signaling in Oryzias latipes - Characterization of inducible oncogene gain-of-function and receptor loss-of-function Medaka lines\n\n" . "text/html" . . . "570 Biowissenschaften, Biologie"@de . "570 Life sciences"@en . .