Lai Karen, Kaspar Brian K, Gage Fred H, Schaffer David V
Department of Chemical Engineering and The Helen Wills Neuroscience Institute, 201 Gilman Hall, University of California, Berkeley, California 94720-1462, USA.
Nat Neurosci. 2003 Jan;6(1):21-7. doi: 10.1038/nn983.
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.
神经干细胞存在于所有哺乳动物的发育中和成年神经系统中，但控制其行为的基本机制尚未完全清楚。在此，我们研究了对神经发育至关重要的因子——音猬因子（Shh）在调节成年海马神经干细胞中的作用。我们发现Shh受体Patched在成年大鼠海马体以及从该区域分离出的神经祖细胞中均有高表达。此外，Shh在体外对祖细胞引发了强烈的、剂量依赖性的增殖反应。再者，将shh cDNA通过腺相关病毒载体导入海马体可使细胞增殖增加3.3倍。最后，Shh信号通路的药理学抑制剂环杷明在体内降低了海马神经祖细胞的增殖。这项研究确定Shh是成年海马神经干细胞的一个调节因子。
