Nature Neuroscience6, 21 - 27 (2002)
Published online: 2 December 2002; | doi:10.1038/nn983
There is a Corrigendum (June 2003) associated with this Article.
Sonic hedgehog regulates adult neural progenitor proliferation in vitro and in vivo
Karen Lai1, Brian K. Kaspar2, Fred H. Gage2
& David V. Schaffer1
1
Department of Chemical Engineering and The Helen Wills Neuroscience Institute, 201 Gilman Hall, University of California, Berkeley, California 94720-1462, USA
2
Laboratory of Genetics, Salk Institute for Biological Studies, Box 85800, San Diego, California 92186-5800, USA
Neural stem cells exist in the developing and adult nervous systems of all mammals, but the basic mechanisms that control their behavior are not yet well understood. Here, we investigated the role of Sonic hedgehog (Shh), a factor vital for neural development, in regulating adult hippocampal neural stem cells. We found high expression of the Shh receptor Patched in both the adult rat hippocampus and neural progenitor cells isolated from this region. In addition, Shh elicited a strong, dose-dependent proliferative response in progenitors in vitro. Furthermore, adeno-associated viral vector delivery of shh cDNA to the hippocampus elicited a 3.3-fold increase in cell proliferation. Finally, the pharmacological inhibitor of Shh signaling cyclopamine reduced hippocampal neural progenitor proliferation in vivo. This work identifies Shh as a regulator of adult hippocampal neural stem cells.
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