title: 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.
authors.affiliation: Department of Brain Development and Neural Regeneration, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
authors.forename: Shinobu
authors.initials: S
authors.lastname: Hirai
authors.forename: Akiko
authors.initials: A
authors.lastname: Miwa
authors.forename: Chiaki
authors.initials: C
authors.lastname: Ohtaka-Maruyama
authors.forename: Masataka
authors.initials: M
authors.lastname: Kasai
authors.forename: Shigeo
authors.initials: S
authors.lastname: Okabe
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Hata
authors.forename: Haruo
authors.initials: H
authors.lastname: Okado
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology*; D002454:Cell Differentiation; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology*; D015870:Gene Expression; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D051796:Inhibitor of Differentiation Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000166:cytology*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D051796:Inhibitor of Differentiation Proteins; D012097:Repressor Proteins; C520669:Zbtb18 protein, mouse