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RP58 controls neuron and astrocyte differentiation by downregulating the expression of Id1–4 genes in the developing cortex
Author(s) -
Hirai Shinobu,
Miwa Akiko,
OhtakaMaruyama Chiaki,
Kasai Masataka,
Okabe Shigeo,
Hata Yutaka,
Okado Haruo
Publication year - 2012
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2011.486
Subject(s) - metropolitan area , library science , medical school , neuroscience , medical education , medicine , biology , computer science , pathology
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 ( i nhibitor of d ifferentiation) 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.