ATF5 regulates the proliferation and differentiation of oligodendrocytes

Jeffrey L. Mason, James M Angelastro, Tatyana N. Ignatova, Valery G. Kukekov, Grace Lin, Lloyd A. Greene, James E. Goldman

Research output: Contribution to journalArticle

51 Scopus citations

Abstract

The transcription factor ATF5 is expressed in cells of the embryonic and neonatal ventricular zone/subventricular zone (VZ/SVZ), and must be down-regulated for their differentiation into neurons and astrocytes. Here, we show that ATF5 plays a major role in directing oligodendrocyte development. ATF5 is expressed by oligodendrocyte precursors but is absent from mature oligodendroglia. Constitutively expressed ATF5 maintains SVZ cells and O4 + oligodendrocyte precursors in cycle and inhibits their differentiation into oligodendrocytes in vitro and in vivo. In contrast, ATF5 loss-of-function (LOF; produced by a dominant-negative form of the protein) accelerates oligodendrocyte differentiation of O4+ cells in vitro and of SVZ cells in vivo. Significantly, the accelerated oligodendrocyte differentiation promoted by ATF5 LOF in vivo results in aberrant migration. Thus, appropriately regulated expression of ATF5 is required for proper expansion of oligodendroglial progenitors as well as for their timely differentiation. Regulation of oligodendrocyte, astrocyte, and neuronal differentiation indicates that ATF5 operates as a general regulator of the timing of differentiation, independent of cell lineage.

Original languageEnglish (US)
Pages (from-to)372-380
Number of pages9
JournalMolecular and Cellular Neuroscience
Volume29
Issue number3
DOIs
StatePublished - Jul 2005
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Developmental Neuroscience

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  • Cite this

    Mason, J. L., Angelastro, J. M., Ignatova, T. N., Kukekov, V. G., Lin, G., Greene, L. A., & Goldman, J. E. (2005). ATF5 regulates the proliferation and differentiation of oligodendrocytes. Molecular and Cellular Neuroscience, 29(3), 372-380. https://doi.org/10.1016/j.mcn.2005.03.004