The basic helix-loop-helix transcription factor olig2 is critical for reactive astrocyte proliferation after cortical injury

J Neurosci. 2008 Oct 22;28(43):10983-9. doi: 10.1523/JNEUROSCI.3545-08.2008.

Abstract

The mechanisms underlying the formation of the glial scar after injury are poorly understood. In this report, we demonstrate that after cortical injury Olig2 is upregulated in reactive astrocytes coincident with proliferation of these cells. Short-term lineage tracing studies with glial subtype-restricted transgenic reporter lines indicate that Olig2-expressing cells in the astroglial but not the oligodendroglial lineage are the essential source of reactive astrocytes. In addition, cortical Olig2 ablation results in a decrease in proliferation of reactive astrocytes in response to injury. Cell-type-specific mutagenesis indicates that Olig2 ablation in GFAP+ astrocytes and their precursors rather than in neuronal or oligodendroglial cells is responsible for the reduction of reactive astrocyte proliferation. Thus, our studies suggest that Olig2 is critical for postinjury gliosis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Astrocytes / physiology*
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / physiology*
  • Brain Injuries / pathology*
  • Cell Lineage
  • Cell Proliferation*
  • Cerebral Cortex / pathology*
  • Gene Expression Regulation / physiology*
  • Glial Fibrillary Acidic Protein / metabolism
  • Intermediate Filament Proteins / metabolism
  • Mice
  • Mice, Mutant Strains
  • Myelin Basic Protein / metabolism
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Nerve Tissue Proteins / physiology*
  • Nestin
  • Oligodendrocyte Transcription Factor 2
  • Receptor, Platelet-Derived Growth Factor alpha / metabolism

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Glial Fibrillary Acidic Protein
  • Intermediate Filament Proteins
  • Myelin Basic Protein
  • Nerve Tissue Proteins
  • Nes protein, mouse
  • Nestin
  • Olig2 protein, mouse
  • Oligodendrocyte Transcription Factor 2
  • Receptor, Platelet-Derived Growth Factor alpha