@article{3d144492e18f4fafa7f66b2059143359,
title = "Sonic hedgehog is required for progenitor cell maintenance in telencephalic stem cell niches",
abstract = "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.",
author = "Robert Machold and Shigemi Hayashi and Michael Rutlin and Muzumdar, {Mandar D.} and Susana Nery and Corbin, {Joshua G.} and Amel Gritli-Linde and Tammy Dellovade and Porter, {Jeffery A.} and Rubin, {Lee L.} and Henryk Dudek and McMahon, {Andrew P.} and Gord Fishell",
note = "Funding Information: We thank Nicholas Gaiano for critical reading of this manuscript and help with in situ hybridizations, as well as Fred Gage for discussion of his recent findings concerning the role of Shh in the hippocampus and advice on hippocampal neuroprogenitor culture. We are also grateful to Ruediger Klein for the gift of Nestin Cre mice and to Paula Lewis for analysis of Shh expression in Shh n/c ;N Cre experiments. We also thank the following people for the gifts of mice, probes, or reagents: A. Joyner (Gli1 LacZ/+ mice), B. Vogelstein (Gli1 probe), M. Scott (Ptch1 probe), F. Guillemot (Mash1; Ngn2 probes), S. Kimura (Nkx2.1 probe), B. Richardson (PDGFRα probe), S. Potter (Gsh2 probe), C. Stiles (Olig2 probe), A. Kawakami (anti-Pax6), K. Campbell (anti-Gsh2), and D. Anderson (Sox10 probe). We also acknowledge the contribution of Yuan Yuan Huang for her technical assistance and Joanne Gensert for her invaluable suggestions concerning our analysis of myelination. Work in G.F.'s laboratory was supported by a NIH grant (NS39007), a March of Dimes basic research grant, and a Children's Brain Tumor Foundation grant to G.F., by a NIH grant to J.G.C. (NS10962-01) and R.M. (1F32NS42525-01). Work in A.P.M.'s laboratory was supported by a grant from the NIH (NS 33642). A.G.L. is supported by the Swedish Medical Research Council grants 2789 and 14100. M.D.M. acknowledges support from the Clarke Fund and a gift from the Zewinski family.",
year = "2003",
month = sep,
day = "11",
doi = "10.1016/S0896-6273(03)00561-0",
language = "English (US)",
volume = "39",
pages = "937--950",
journal = "Neuron",
issn = "0896-6273",
publisher = "Cell Press",
number = "6",
}