<> "The repository administrator has not yet configured an RDF license."^^ . <> . . "Regulation of Adult Neural Stem Cell Activation\r\nby Orphan Nuclear Receptor TLX (NR2E1)\r\nand Notch Signaling"^^ . "The adult mammalian brain contains neural stem cells (NSCs) that continue to generate\r\nneurons throughout adulthood, a process referred to as neurogenesis. Adult NSCs are\r\nrelatively quiescent and undergo cell division only when they are activated to reenter the cell\r\ncycle. Two types of quiescent NSCs have been previously identified, which can be\r\ndistinguished on the basis of differential expression of Prominin-1 (Pro). Upon activation and\r\nasymmetrical division, a NSC self-renews and gives rise to a transit-amplifying precursor\r\n(TAP), which will rapidly divide while differentiating into neuroblasts. Our group has developed\r\nan approach based on fluorescence activated cell sorting (FACS) to purify quiescent NSCs\r\n(qNSCs), activated NSCs (aNSCs) and TAPs.\r\nWe have previously shown that in adult NSCs the orphan nuclear receptor Tailless (Tlx,\r\nNR2E1) is essential for promoting cell cycle entry and the transition from qNSCs to aNSCs.\r\nTherefore, mice lacking Tlx expression (Tlx-/-) represent a nice model system to investigate the\r\nmechanisms underlying NSC activation. To further understand the molecular mechanisms\r\nunderlying the effect of TLX on NSC activation I have compared gene expression in NSCs\r\nisolated from wild type (WT) and Tlx-/- mice. This analysis revealed an upregulation of Hes1\r\nexpression and a significant change in the expression of several genes associated to the\r\nNotch pathway in both Pro+ and Pro- mutant qNSCs. Moreover, in the absence of TLX, the\r\nnuclear localization of the Notch intracellular domain (NICD) was increased in Pro- qNSCs,\r\nsuggesting hyper activation of the canonical Notch pathway, which may prevent cell cycle\r\nentry. To provide support for this hypothesis, I have investigated the effect of pharmacological\r\ninhibition of Notch signaling on NSC activation. These experiments revealed that indeed\r\nblockade of Notch signaling increased proliferation of both WT and Tlx-/- precursors. They also\r\nshowed that inhibition of Notch signaling leads to the generation of Pro+ qNSCs from the Procell\r\npool, suggesting a lineage relationship between the two groups of qNSCs. Since TLX is\r\na transcriptional repressor, it may modulate Notch signaling by repressing the expression of\r\nHes1. To further investigate this hypothesis I have taken advantage of luciferase and\r\nchromatin immunoprecipitation (ChIP) assays and I was able to show that TLX represses\r\nHes1 expression and that this effect requires the presence of the RBPJ binding site.\r\nTaken together, my results have uncovered a previously unknown function of TLX in the\r\nregulation of Hes1 expression, which affects the activation of the canonical Notch pathway in\r\nNSCs and also the progression from Pro- to Pro+ qNSCs."^^ . "2015" . . . . . . . "Yan"^^ . "Shi"^^ . "Yan Shi"^^ . . . . . . "Regulation of Adult Neural Stem Cell Activation\r\nby Orphan Nuclear Receptor TLX (NR2E1)\r\nand Notch Signaling (PDF)"^^ . . . "Dissertation for print
.pdf"^^ . . . "Regulation of Adult Neural Stem Cell Activation\r\nby Orphan Nuclear Receptor TLX (NR2E1)\r\nand Notch Signaling (Other)"^^ . . . . . . "lightbox.jpg"^^ . . . "Regulation of Adult Neural Stem Cell Activation\r\nby Orphan Nuclear Receptor TLX (NR2E1)\r\nand Notch Signaling (Other)"^^ . . . . . . "preview.jpg"^^ . . . "Regulation of Adult Neural Stem Cell Activation\r\nby Orphan Nuclear Receptor TLX (NR2E1)\r\nand Notch Signaling (Other)"^^ . . . . . . "medium.jpg"^^ . . . "Regulation of Adult Neural Stem Cell Activation\r\nby Orphan Nuclear Receptor TLX (NR2E1)\r\nand Notch Signaling (Other)"^^ . . . . . . "small.jpg"^^ . . . "Regulation of Adult Neural Stem Cell Activation\r\nby Orphan Nuclear Receptor TLX (NR2E1)\r\nand Notch Signaling (Other)"^^ . . . . . . "indexcodes.txt"^^ . . "HTML Summary of #18941 \n\nRegulation of Adult Neural Stem Cell Activation \nby Orphan Nuclear Receptor TLX (NR2E1) \nand Notch Signaling\n\n" . "text/html" . . . "570 Biowissenschaften, Biologie"@de . "570 Life sciences"@en . .