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The EMBO Journal
Article . 2012

RP58 controls neuron and astrocyte differentiation by downregulating the expression of Id1-4 genes in the developing cortex.

Authors: Shinobu, Hirai; Akiko, Miwa; Chiaki, Ohtaka-Maruyama; Masataka, Kasai; Shigeo, Okabe; Yutaka, Hata; Haruo, Okado;

RP58 controls neuron and astrocyte differentiation by downregulating the expression of Id1-4 genes in the developing cortex.

Abstract

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.

Keywords

Cerebral Cortex, Mice, Knockout, Neurons, Repressor Proteins, Mice, Gene Expression Regulation, Astrocytes, Gene Knockdown Techniques, Animals, Gene Expression, Cell Differentiation, Inhibitor of Differentiation Proteins

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Powered by OpenAIRE graph
citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
42
Top 10%
Top 10%
Top 10%