title: Brg1 is required for murine neural stem cell maintenance and gliogenesis.
abstract: Epigenetic alterations in cell-type-specific gene expression control the transition of neural stem cells (NSCs) from predominantly neurogenic to predominantly gliogenic phases of differentiation, but how this switch occurs is unclear. Here, we show that brahma-related gene 1 (Brg1), an ATP-dependent chromatin remodeling factor, is required for the repression of neuronal commitment and the maintenance of NSCs in a state that permits them to respond to gliogenic signals. Loss of Brg1 in NSCs in conditional brg1 mutant mice results in precocious neuronal differentiation, such that cells in the ventricular zone differentiate into post-mitotic neurons before the onset of gliogenesis. As a result, there is a dramatic failure of astrocyte and oligodendrocyte differentiation in these animals. The ablation of brg1 in gliogenic progenitors in vitro also prevents growth-factor-induced astrocyte differentiation. Furthermore, proteins implicated in the maintenance of stem cells, including Sox1, Pax6 and Musashi-1, are dramatically reduced in the ventricular zones of brg1 mutant mice. We conclude that Brg1 is required to repress neuronal differentiation in NSCs as a means of permitting glial cell differentiation in response to gliogenic signals, suggesting that Brg1 regulates the switch from neurogenesis to gliogenesis.
authors.affiliation: Integrative Biosciences Department, School of Dentistry, Oregon Health and Science University, Portland, 97239, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Matsumoto
authors.forename: Fatima
authors.initials: F
authors.lastname: Banine
authors.forename: Jaime
authors.initials: J
authors.lastname: Struve
authors.forename: Rubing
authors.initials: R
authors.lastname: Xing
authors.forename: Chris
authors.initials: C
authors.lastname: Adams
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Daniel
authors.initials: D
authors.lastname: Metzger
authors.forename: Pierre
authors.initials: P
authors.lastname: Chambon
authors.forename: Mahendra S
authors.initials: MS
authors.lastname: Rao
authors.forename: Larry S
authors.initials: LS
authors.lastname: Sherman
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000378:metabolism; D004265:DNA Helicases; D005260:Female; D018507:Gene Expression Regulation, Developmental; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D038081:Organogenesis / Q000502:physiology*; D010641:Phenotype; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
chemical_list: D009687:Nuclear Proteins; D014157:Transcription Factors; C513194:Smarca4 protein, mouse; D004265:DNA Helicases