Genetic Activation of Hedgehog Signaling Unbalances the Rate of Neural Stem Cell Renewal by Increasing Symmetric Divisions
Genetic Activation of Hedgehog Signaling Unbalances the Rate of Neural Stem Cell Renewal by Increasing Symmetric Divisions
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DOI：
10.1016/j.stemcr.2014.05.016
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发表时间：
2014-08-12
影响因子：
5.9
通讯作者：
Traiffort, Elisabeth
中科院分区：
文献类型：
--
作者：
Ferent, Julien;Cochard, Loic;Traiffort, Elisabeth
在成人大脑中，自我更新对于神经干细胞（NSCs）在整个生命过程中的持续存在至关重要，但其调控机制仍然知之甚少。一个NSC可以产生两个NSC或一个NSC和一个瞬时祖细胞。一个正确的平衡是维持生发区所必需的，理解NSC分裂模式的分子机制显然是重要的。在这里，我们报道了Sonic Hedgehog （SHH）受体补丁在室管膜下区直接控制长期NSC自我更新的功能。我们发现，成年NSCs中SHH信号的遗传条件激活导致它们的扩增和直接后代的消耗。这些表型在体外与涉及NOTCH信号的过程中NSC对称分裂的增加有关。综上所述，我们的研究结果证明了补丁驱动的成人神经发生和NSC更新的严格控制。
In the adult brain, self-renewal is essential for the persistence of neural stem cells (NSCs) throughout life, but its regulation is still poorly understood. One NSC can give birth to two NSCs or one NSC and one transient progenitor. A correct balance is necessary for the maintenance of germinal areas, and understanding the molecular mechanisms underlying NSC division mode is clearly important. Here, we report a function of the Sonic Hedgehog (SHH) receptor Patched in the direct control of long-term NSC self-renewal in the subependymal zone. We show that genetic conditional activation of SHH signaling in adult NSCs leads to their expansion and the depletion of their direct progeny. These phenotypes are associated in vitro with an increase in NSC symmetric division in a process involving NOTCH signaling. Together, our results demonstrate a tight control of adult neurogenesis and NSC renewal driven by Patched.