期刊
VISION RESEARCH
卷 51, 期 2, 页码 251-259出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.visres.2010.10.016
关键词
Retinal development; Retinal progenitor cells; Retinal ganglion cells; Cell cycle; Homeobox factor Pax6; Proneural bHLH factors Atoh7; Neurod1
资金
- NCI NIH HHS [P30 CA016672, CA016672] Funding Source: Medline
- NEI NIH HHS [R21 EY019015, EY011930, EY010608-139005, P30 EY010608, R01 EY011930] Funding Source: Medline
Retinal progenitor cells (RPCs) are programmed early in development to acquire the competence for specifying the seven retinal cell types. Acquiring competence is a complex spatiotemporal process that is still only vaguely understood. Here, our objective was to more fully understand the mechanisms by which RPCs become competent for specifying a retinal ganglion cell (RGC) fate. RGCs are the first retinal cell type to differentiate and their abnormal development leads to apoptosis and optic nerve degeneration. Previous work demonstrated that the paired domain factor Pax6 and the bHLH factor Atoh7 are required for RPCs to specify RGCs. RGC commitment is marked by the expression of the Pou domain factor Pou4f2 and the Lim domain factor Isl1. We show that three RPC subpopulations can specify RGCs: Atoh7-expressing RPCs, Neurod1-expressing RPCs, and Atoh7-Neurod1-expressing RPCs. All three RPC subpopulations were highly interspersed throughout retinal development, although each subpopulation maintained a distinct temporal pattern. Most, but not all, RPCs from each subpopulation were postmitotic. Atoh7-Neurod1 double knockout mice were generated and double-mutant retinas revealed an unexpected role for Neurod1 in specifying RGC fate. We conclude that RPCs have a complex regulatory gene expression program in which they acquire competence using highly integrated mechanisms. (C) 2010 Elsevier Ltd. All rights reserved.
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