<> "The repository administrator has not yet configured an RDF license."^^ . <> . . "Cell intrinsic control of stem cell features in the retina"^^ . "Post-embryonic neurogenesis relies on the presence of neural stem cells, which are characterized by\r\ntheir multipotency and unique ability to self-renew. Despite their importance for the homeostasis and\r\nrepair of the central nervous system, the transcriptional network governing stemness in adult neural\r\nstem cells is largely unknown.\r\nWe established the transcription factor Rx2 as proxy for retinal stem cells in the post-embryonic retina\r\nof the teleost medaka (O. latipes). By interrogating the regulatory input to the Rx2 cis-regulatory\r\nelement, we identified four transcription factors (Sox2, Tlx, Gli3, Her9), which distinctly shape the stem\r\ncell domain and modulate stem cell features in the retina. First of all, we analyzed the gene expression\r\nand found that these genes have distinct spatio-temporal expression patterns in the retinal stem cell\r\ndomain. Conditional mosaic analysis in vivo confirmed Sox2 and Tlx as activators of Rx2. The ectopic\r\nexpression of Sox2 or Tlx was sufficient to trigger de-differentiation of post-mitotic neurons and induced\r\nstem cell features therein. Conversely, sustained ectopic expression of Gli3 or Her9 repressed Rx2.\r\nGain of Gli3 or Her9 in retinal stem cells arrested cell cycle progression and proliferation. Modification\r\nof conserved binding sites in the Rx2 cis-regulatory element revealed the importance of Sox and Gli\r\ntranscription factors for the precise spatial Rx2 expression in retinal stem cells. We propose that the\r\ncombinatorial regulatory input of Sox2, Tlx, Gli3, Her9 confines Rx2 expression and other features of\r\nretinal stem cells specifically to the periphery of the stem cell domain in the post-embryonic retina.\r\nTo elucidate the functional role of Rx2 itself, mutants were established with the aid of targetable\r\nnucleases. Transcription activator-like effector nucleases were employed to induce double-strand\r\nbreaks specifically in the Rx2 coding sequence, which in the case of erroneous non-homologous\r\nend-joining created sequence alterations at the site of cleavage. The generation of stable, heritable\r\nmutations in the endogenous Rx2 locus described here opens the opportunity for future genetic studies\r\nof Rx2 in medaka."^^ . "2014" . . . . . . . "Robert"^^ . "Reinhardt"^^ . "Robert Reinhardt"^^ . . . . . . "Cell intrinsic control of stem cell features in the retina (PDF)"^^ . . . "Robert_Reinhardt_2014_red.pdf"^^ . . . "Cell intrinsic control of stem cell features in the retina (Other)"^^ . . . . . . "indexcodes.txt"^^ . . . "Cell intrinsic control of stem cell features in the retina (Other)"^^ . . . . . . "lightbox.jpg"^^ . . . "Cell intrinsic control of stem cell features in the retina (Other)"^^ . . . . . . "preview.jpg"^^ . . . "Cell intrinsic control of stem cell features in the retina (Other)"^^ . . . . . . "medium.jpg"^^ . . . "Cell intrinsic control of stem cell features in the retina (Other)"^^ . . . . . . "small.jpg"^^ . . "HTML Summary of #16650 \n\nCell intrinsic control of stem cell features in the retina\n\n" . "text/html" . . . "000 Allgemeines, Wissenschaft, Informatik"@de . "000 Generalities, Science"@en . .