Connexin expression by radial glia-like cells is required for neurogenesis in the adult dentate gyrus

Proc Natl Acad Sci U S A. 2009 Jul 7;106(27):11336-41. doi: 10.1073/pnas.0813160106. Epub 2009 Jun 22.

Abstract

In the adult dentate gyrus, radial glia-like cells represent putative stem cells generating neurons and glial cells. Here, we combined patch-clamp recordings, biocytin filling, immunohistochemistry, single-cell transcript analysis, and mouse transgenics to test for connexin expression and gap junctional coupling of radial glia-like cells and its impact on neurogenesis. Radial glia-like cells were identified in mice expressing EGFP under control of the nestin and gfap promoters. We show that a majority of Radial glia-like cells are coupled and express Cx43. Neuronal precursors were not coupled. Mice lacking Cx30 and Cx43 in GFAP-positive cells displayed almost complete inhibition of proliferation and a significant decline in numbers of radial glia-like cells and granule neurons. Inducible virus-mediated ablation of connexins in the adult hippocampus also reduced neurogenesis. These findings strongly suggest the requirement of connexin expression by radial glia-like cells for intact neurogenesis in the adult brain and point to possible communication pathways of these cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bromodeoxyuridine / metabolism
  • Cell Count
  • Cell Proliferation
  • Connexin 30
  • Connexin 43 / metabolism*
  • Connexins / metabolism*
  • Cytoplasmic Granules / metabolism
  • Dentate Gyrus / cytology
  • Dentate Gyrus / metabolism*
  • Gap Junctions / metabolism
  • Gene Deletion
  • Humans
  • Lysine / analogs & derivatives
  • Lysine / metabolism
  • Mice
  • Mice, Knockout
  • Neurogenesis*
  • Neuroglia / cytology
  • Neuroglia / metabolism*
  • Protein Isoforms / metabolism

Substances

  • Connexin 30
  • Connexin 43
  • Connexins
  • Gjb6 protein, mouse
  • Protein Isoforms
  • Bromodeoxyuridine
  • biocytin
  • Lysine