Increased expression of Nkx2.2 and Olig2 identifies reactive oligodendrocyte progenitor cells responding to demyelination in the adult CNS

Mol Cell Neurosci. 2004 Nov;27(3):247-54. doi: 10.1016/j.mcn.2004.06.015.

Abstract

Within the adult CNS, a quiescent population of oligodendrocyte progenitor cells (OPCs) become activated in response to demyelination and give rise to remyelinating oligodendrocytes. During development, OPC differentiation is controlled by several transcription factors including Olig1 and Olig2, and Nkx2.2. We hypothesized that these genes may serve similar functions in activated adult OPCs allowing them to become remyelinating oligodendrocytes and tested this hypothesis by examining their expression during the remyelination of a toxin-induced rodent model of demyelination. During the acute phase of demyelination, OPCs within the lesion increased their expression of Nkx2.2 and Olig2, two transcription factors that in combination are critical for oligodendrocyte differentiation during developmental myelination. This activation was not associated with increases in Sonic hedgehog (Shh) expression, which does not appear essential for CNS remyelination. Consistent with a role in the activation and differentiation of OPCs, these increases were delayed in old adult animals where the rate of remyelination is slowed. Our data suggest the hypothesis that increased expression of Nkx2.2 and Olig2 plays a critically important role in the differentiation of adult OPCs into remyelinating oligodendrocytes and that these genes may present novel targets for therapeutic manipulation in cases where remyelination is impaired.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors
  • Central Nervous System / cytology
  • Central Nervous System / metabolism
  • Demyelinating Diseases / metabolism*
  • Demyelinating Diseases / pathology
  • Female
  • Gene Expression Regulation / physiology
  • Homeodomain Proteins / biosynthesis*
  • Nerve Tissue Proteins / biosynthesis*
  • Oligodendroglia / cytology
  • Oligodendroglia / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Stem Cells / cytology
  • Stem Cells / metabolism*
  • Transcription Factors / biosynthesis*
  • Up-Regulation
  • Zebrafish Proteins

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Homeodomain Proteins
  • Nerve Tissue Proteins
  • Nkx2.2 protein
  • Transcription Factors
  • Zebrafish Proteins