Journal
EMBO JOURNAL
Volume 31, Issue 5, Pages 1190-1202Publisher
WILEY
DOI: 10.1038/emboj.2011.486
Keywords
cell cycle control; cortical development; cyclin-dependent kinase inhibitor; fate of NSCs; p57
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Funding
- Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan
- Ministry of Education
- Grants-in-Aid for Scientific Research [22650070, 23123523, 22590267] Funding Source: KAKEN
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Appropriate number of neurons and glial cells is generated from neural stem cells (NSCs) by the regulation of cell cycle exit and subsequent differentiation. Although the regulatory mechanism remains obscure, Id (inhibitor of differentiation) proteins are known to contribute critically to NSC proliferation by controlling cell cycle. Here, we report that a transcriptional factor, RP58, negatively regulates all four Id genes (Id1-Id4) in developing cerebral cortex. Consistently, Rp58 knockout (KO) mice demonstrated enhanced astrogenesis accompanied with an excess of NSCs. These phenotypes were mimicked by the overexpression of all Id genes in wild-type cortical progenitors. Furthermore, Rp58 KO phenotypes were rescued by the knockdown of all Id genes in mutant cortical progenitors but not by the knockdown of each single Id gene. Finally, we determined p57 as an effector gene of RP58-Id-mediated cell fate control. These findings establish RP58 as a novel key regulator that controls the self-renewal and differentiation of NSCs and restriction of astrogenesis by repressing all Id genes during corticogenesis. The EMBO Journal (2012) 31, 1190-1202. doi: 10.1038/emboj.2011.486; Published online 10 January 2012
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