Sonic hedgehog regulates adult neural progenitor proliferation in vitro and in vivo
Sonic hedgehog regulates adult neural progenitor proliferation in vitro and in vivo
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DOI：
10.1038/nn983
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发表时间：
2003-01-01
影响因子：
25
通讯作者：
Schaffer, DV
中科院分区：
文献类型：
--
作者：
Lai, K;Kaspar, BK;Schaffer, DV
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不清楚。在这里，我们研究了音刺猬（Shh）（对神经发育至关重要的因子）在调节成年海马神经干细胞中的作用。我们发现成年大鼠海马体和从该区域分离的神经祖细胞中都有高表达的 Shh 受体 Patched。此外，Shh 在体外祖细胞中引发了强烈的、剂量依赖性的增殖反应。此外，将 shh cDNA 的腺相关病毒载体递送至海马体可使细胞增殖增加 3.3 倍。最后，Shh 信号传导的药理学抑制剂环巴明减少了体内海马神经祖细胞的增殖。这项工作将 Shh 确定为成人海马神经干细胞的调节者。
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.