Sonic hedgehog expands neural stem cells in the neocortical region leading to an expanded and wrinkled neocortical surface

Sonic hedgehog expands neural stem cells in the neocortical region leading to an expanded and wrinkled neocortical surface
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Sonic hedgehog基因扩展新皮质区域的神经干细胞,导致新皮质表面扩大和起皱

DOI:
10.1111/gtc.12847
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发表时间:
2021-04
期刊:
影响因子:
2.1
通讯作者:
Mohammed Shqirat;Akira Kinoshita;R. Kageyama;T. Ohtsuka
Mohammed Shqirat;Akira Kinoshita;R. Kageyama;T. Ohtsuka
中科院分区:
生物学4区
文献类型:
--
作者:
Mohammed Shqirat;Akira Kinoshita;R. Kageyama;T. Ohtsuka

文献摘要

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扩张和折叠的新皮层是高等哺乳动物的特征,包括人类和其他灵长类动物。在哺乳动物的大脑从无脑到回脑的进化过程中,新皮层表面积急剧扩大,这赋予了更高的认知功能,特别是灵长类动物,包括人类。在这项研究中,我们产生了转基因(Tg)小鼠,其中可以通过使用泰特-on系统在神经干细胞(NSCs)和神经祖细胞中控制Sonic hedgehog(Shh)的表达。Shh在胚胎发育过程中的过度表达促进了神经干细胞在新皮层区域的对称性增殖分裂,导致侧脑室扩大和脑室区的切线延伸。此外,Shh-过表达的Tg小鼠表现出新皮层表面积的急剧扩张,并且当在神经发育的早期阶段开始过表达时,表现出皱纹的大脑。这些结果表明,Shh能够增加新皮层NSC并有助于新皮层的扩展。
An expanded and folded neocortex is characteristic of higher mammals, including humans and other primates. The neocortical surface area was dramatically enlarged during the course of mammalian brain evolution from lissencephalic to gyrencephalic mammals, and this bestowed higher cognitive functions especially to primates, including humans. In this study, we generated transgenic (Tg) mice in which the expression of Sonic hedgehog (Shh) could be controlled in neural stem cells (NSCs) and neural progenitors by using the Tet‐on system. Shh overexpression during embryogenesis promoted the symmetric proliferative division of NSCs in the neocortical region, leading to the expansion of lateral ventricles and tangential extension of the ventricular zone. Moreover, Shh‐overexpressing Tg mice showed dramatic expansion of the neocortical surface area and exhibited a wrinkled brain when overexpression was commenced at early stages of neural development. These results indicate that Shh is able to increase the neocortical NSCs and contribute to expansion of the neocortex.