Regulated expression of ATF5 is required for the progression of neural progenitor cells to neurons

James M Angelastro, Tatyana N. Ignatova, Valery G. Kukekov, Dennis A. Steindler, George B. Stengren, Cathy Mendelsohn, Lloyd A. Greene

Research output: Contribution to journalArticle

100 Scopus citations

Abstract

An important milestone in brain development is the transition of neuroprogenitor cells to postmitotic neurons. We report that the bZIP transcription factor ATF5 plays a major regulatory role in this process. In developing brain ATF5 expression is high within ventricular zones containing neural stem and progenitor cells and is undetectable in postmitotic neurons. In attached clonal neurosphere cultures ATF5 is expressed by neural stem/progenitor cells and is undetectable in tau-positive neurons. In PC 12 cell cultures nerve growth factor (NGF) dramatically downregulates endogenous ATF5 protein and transcripts, whereas exogenous ATF5 suppresses NGF-promoted neurite outgrowth. Such inhibition requires the repression of CRE sites. In contrast, loss of function conferred by dominant-negative ATF5 accelerates NGF-promoted neuritogenesis. Exogenous ATF5 also suppresses, and dominant-negative ATF5 and a small-interfering RNA targeted to ATF5 promote, neurogenesis by cultured nestin-positive telencephalic cells. These findings indicate that ATF5 blocks the differentiation of neuroprogenitor cells into neurons and must be downregulated to permit this process to occur.

Original languageEnglish (US)
Pages (from-to)4590-4600
Number of pages11
JournalJournal of Neuroscience
Volume23
Issue number11
StatePublished - Jun 1 2003
Externally publishedYes

Keywords

  • ATF5
  • Differentiation
  • Neural progenitor cells
  • Neuron
  • NGF
  • Ventricular zone

ASJC Scopus subject areas

  • Neuroscience(all)

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  • Cite this

    Angelastro, J. M., Ignatova, T. N., Kukekov, V. G., Steindler, D. A., Stengren, G. B., Mendelsohn, C., & Greene, L. A. (2003). Regulated expression of ATF5 is required for the progression of neural progenitor cells to neurons. Journal of Neuroscience, 23(11), 4590-4600.