Connexin expression by radial glia-like cells is required for neurogenesis in the adult dentate gyrus.
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.
Kunze
Albrecht
A
Institute of Cellular Neurosciences, Medical Faculty, University of Bonn, Sigmund-Freud-Strasse 25, 53105 Bonn, Germany.
Congreso
Marga Rubenecia
MR
Hartmann
Christian
C
Wallraff-Beck
Anke
A
Hüttmann
Kerstin
K
Bedner
Peter
P
Requardt
Robert
R
Seifert
Gerald
G
Redecker
Christoph
C
Willecke
Klaus
K
Hofmann
Andreas
A
Pfeifer
Alexander
A
Theis
Martin
M
Steinhäuser
Christian
C
D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count; D049109:Cell Proliferation; D000075302:Connexin 30; D018031:Connexin 43 / Q000378:metabolism*; D017630:Connexins / Q000378:metabolism*; D003594:Cytoplasmic Granules / Q000378:metabolism; D018891:Dentate Gyrus / Q000166:cytology / Q000378:metabolism*; D017629:Gap Junctions / Q000378:metabolism; D017353:Gene Deletion; D006801:Humans; D008239:Lysine / Q000031:analogs & derivatives / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D055495:Neurogenesis; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism
D000075302:Connexin 30; D018031:Connexin 43; D017630:Connexins; C100629:Gjb6 protein, mouse; D020033:Protein Isoforms; D001973:Bromodeoxyuridine; C013411:biocytin; D008239:Lysine