Downregulation of activating transcription factor 5 is required for differentiation of neural progenitor cells into astrocytes

James M Angelastro, Jeffrey L. Mason, Tatyana N. Ignatova, Valery G. Kukekov, George B. Stengren, James E. Goldman, Lloyd A. Greene

Research output: Contribution to journalArticle

63 Scopus citations

Abstract

The mechanisms that regulate neural progenitor cell differentiation are primarily unknown. The transcription factor activating transcription factor 5 (ATF5) is expressed in neural progenitors of developing brain but is absent from mature astrocytes and neurons. Here, we demonstrate that ATF5 regulates the conversion of ventricular zone (VZ) and subventricular zone (SVZ) neural progenitors into astrocytes. Constitutive ATF5 expression maintains neural progenitor cell proliferation and blocks their in vitro and in vivo differentiation into astrocytes. Conversely, loss of ATF5 function promotes cell-cycle exit and allows astrocytic differentiation in vitro and in vivo. CNTF, a promoter of astrocytic differentiation, downregulates endogenous ATF5, whereas constitutively expressed ATF5 suppresses CNTF-promoted astrocyte genesis. Unexpectedly, constitutive ATF5 expression in neonatal SVZ cells both in vitro and in vivo causes them to acquire properties and anatomic distributions of VZ cells. These findings identify ATF5 as a key regulator of astrocyte formation and potentially of the VZ to SVZ transition.

Original languageEnglish (US)
Pages (from-to)3889-3899
Number of pages11
JournalJournal of Neuroscience
Volume25
Issue number15
DOIs
StatePublished - Apr 13 2005

Keywords

  • Astrocyte
  • ATF5
  • CNTF
  • Neural progenitor cells
  • Neuron
  • Ventricular zone

ASJC Scopus subject areas

  • Neuroscience(all)

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