Brg1 is required for murine neural stem cell maintenance and gliogenesis

Steven Matsumoto, Fatima Banine, Jaime Struve, Rubing Xing, Chris Adams, Ying Liu, Daniel Metzger, Pierre Chambon, Mahendra S. Rao, Larry S. Sherman

Research output: Contribution to journalArticle

101 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)372-383
Number of pages12
JournalDevelopmental Biology
Volume289
Issue number2
DOIs
StatePublished - Jan 15 2006

Keywords

  • Astrocytes
  • Brg1
  • Chromatin remodeling
  • Neural stem cells
  • Neurons
  • Oligodendrocytes

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Brg1 is required for murine neural stem cell maintenance and gliogenesis'. Together they form a unique fingerprint.

  • Cite this