Oligodendrocyte progenitor enrichment in the connexin32 null-mutant mouse

J Neurosci. 2003 Mar 1;23(5):1759-68. doi: 10.1523/JNEUROSCI.23-05-01759.2003.

Abstract

Before the establishment of chemical synapses, neural progenitors are often coupled by connexin-mediated gap junctions providing a robust mechanism for cell-cell communication in developing brain. The present study was undertaken to determine whether alterations in junctional coupling also affect neural progenitor proliferation, survival, and differentiation in adult brain. We localized the connexin32 gap junction protein to a subset of NG2+ and platelet-derived growth factor alpha receptor+ early oligodendrocyte progenitors in the dentate gyrus of adult mice. In connexin32-deficient mice, we found an increase in the total number of proliferating nestin+ and NG2+ progenitors in the subgranular zone, hilus, and polymorphonuclear layer of the dentate gyrus in vivo and in the total number of nestin+ progenitors capable of clonogenic expansion in vitro. By bromodeoxyuridine labeling, lineage analysis, and terminal deoxynucleotidyl nick end labeling, we demonstrate that turnover of these cells is constitutively enhanced in the connexin32 knock-out dentate gyrus reflecting a dynamic defect in oligodendrogenesis in this population. Analyses of surviving bromodeoxyuridine-labeled cells at 1, 3, 7, and 28 d after injection demonstrate that this transient amplifying population fails to terminally differentiate and is deleted by an apoptotic-like mechanism within 3 d of labeling. These data provide empirical evidence to support the hypothesis that connexin expression influences adult progenitor number and specifically implicate connexin32-mediated signaling in the activation, survival, and differentiation of a subset of early oligodendrocyte progenitors in postnatal brain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Bromodeoxyuridine
  • Cell Count
  • Cell Differentiation / physiology
  • Cell Division
  • Cell Survival
  • Connexins / biosynthesis
  • Connexins / deficiency*
  • Connexins / genetics
  • Dentate Gyrus / cytology*
  • Dentate Gyrus / growth & development*
  • Glial Fibrillary Acidic Protein / biosynthesis
  • In Situ Nick-End Labeling
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Mutant Strains
  • Oligodendroglia / cytology*
  • Oligodendroglia / metabolism
  • Stem Cells / cytology*
  • Stem Cells / metabolism

Substances

  • Connexins
  • Glial Fibrillary Acidic Protein
  • connexin 32
  • Bromodeoxyuridine