Sonic hedgehog regulates adult neural progenitor proliferation in vitro and in vivo.
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.
Lai
Karen
K
Department of Chemical Engineering and The Helen Wills Neuroscience Institute, 201 Gilman Hall, University of California, Berkeley, California 94720-1462, USA.
Kaspar
Brian K
BK
Gage
Fred H
FH
Schaffer
David V
DV
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics*; D002455:Cell Division / Q000187:drug effects / Q000235:genetics*; D002478:Cells, Cultured; D005260:Female; D005455:Fluorescent Antibody Technique; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000235:genetics; D053823:Hedgehog Proteins; D006624:Hippocampus / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D066298:In Vitro Techniques; D008565:Membrane Proteins / Q000378:metabolism; D009473:Neuronal Plasticity / Q000187:drug effects / Q000235:genetics; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000072079:Patched Receptors; D051381:Rats; D011916:Rats, Inbred F344; D011956:Receptors, Cell Surface; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015534:Trans-Activators / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
D053823:Hedgehog Proteins; D008565:Membrane Proteins; D000072079:Patched Receptors; D011956:Receptors, Cell Surface; D015534:Trans-Activators