The Journal of Neuroscience, March 1, 2003, 23(5):1759
Oligodendrocyte Progenitor Enrichment in the Connexin32
Null-Mutant Mouse
Lysanne
Melanson-Drapeau1,
Sandy
Beyko1,
Shefali
Davé1,
Andrea L. O.
Hebb1,
Doug J.
Franks2,
Caterina
Sellitto3,
David L.
Paul3, and
Steffany A. L.
Bennett1
1 Neural Regeneration Laboratory, Department of
Biochemistry, Microbiology, and Immunology and 2 Department
of Pathology, University of Ottawa, Ottawa, Ontario, K1H 8M5 Canada,
and 3 Department of Neurobiology, Harvard Medical School,
Boston, Massachusetts 02115
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
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.
Key words:
connexin; knock-out; stem cell; gap junction; progenitor; connexin32
Copyright © 2003 Society for Neuroscience 0270-6474/03/2351759-10$05.00/0
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