Ferent Julien, Cochard Loïc, Faure Hélène, Taddei Maurizio, Hahn Heidi, Ruat Martial, Traiffort Elisabeth
Laboratory of Neurobiology and Development-CNRS, Signal Transduction and Developmental Neuropharmacology Team, Institute of Neurobiology Alfred Fessard, Gif-sur-Yvette 91198, France.
Dipartimento Farmaco Chimico Tecnologico, Università degli Studi di Siena, 53100 Siena, Italy.
Stem Cell Reports. 2014 Aug 12;3(2):312-23. doi: 10.1016/j.stemcr.2014.05.016. Epub 2014 Jun 19.
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.
在成人大脑中，自我更新对于神经干细胞（NSC）终身存在至关重要，但其调控机制仍知之甚少。一个神经干细胞可以产生两个神经干细胞，或者一个神经干细胞和一个短暂祖细胞。维持生发区需要正确的平衡，因此了解神经干细胞分裂模式背后的分子机制显然很重要。在这里，我们报告了音猬因子（SHH）受体Patched在直接控制室管膜下区神经干细胞长期自我更新中的作用。我们发现，成年神经干细胞中SHH信号的基因条件性激活会导致其数量增加以及其直接子代细胞的耗竭。在体外，这些表型与涉及NOTCH信号传导的过程中神经干细胞对称分裂的增加有关。总之，我们的结果表明Patched对成年神经发生和神经干细胞更新具有严格的调控作用。
