Sonic hedgehog is required for progenitor cell maintenance in telencephalic stem cell niches.
To directly test the requirement for hedgehog signaling in the telencephalon from early neurogenesis, we examined conditional null alleles of both the Sonic hedgehog and Smoothened genes. While the removal of Shh signaling in these animals resulted in only minor patterning abnormalities, the number of neural progenitors in both the postnatal subventricular zone and hippocampus was dramatically reduced. In the subventricular zone, this was partially attributable to a marked increase in programmed cell death. Consistent with Hedgehog signaling being required for the maintenance of stem cell niches in the adult brain, progenitors from the subventricular zone of floxed Smo animals formed significantly fewer neurospheres. The loss of hedgehog signaling also resulted in abnormalities in the dentate gyrus and olfactory bulb. Furthermore, stimulation of the hedgehog pathway in the mature brain resulted in elevated proliferation in telencephalic progenitors. These results suggest that hedgehog signaling is required to maintain progenitor cells in the postnatal telencephalon.
Machold
Robert
R
Developmental Genetics Program and Department of Cell Biology, The Skirball Institute of Biomolecular Medicine, New York University Medical Center, 540 First Avenue, New York, NY 10016, USA.
Hayashi
Shigemi
S
Rutlin
Michael
M
Muzumdar
Mandar D
MD
Nery
Susana
S
Corbin
Joshua G
JG
Gritli-Linde
Amel
A
Dellovade
Tammy
T
Porter
Jeffery A
JA
Rubin
Lee L
LL
Dudek
Henryk
H
McMahon
Andrew P
AP
Fishell
Gord
G
D000818:Animals; D016923:Cell Death / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D053823:Hedgehog Proteins; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D013687:Telencephalon / Q000166:cytology / Q000196:embryology / Q000378:metabolism* / Q000502:physiology; D015534:Trans-Activators / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*
D053823:Hedgehog Proteins; C465570:Shh protein, mouse; D015534:Trans-Activators