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时松海和史航团队发现中心体的锚定调控祖细胞特性和大脑皮层形成
作者:小柯机器人 发布时间:2020/3/29 23:51:04

清华大学时松海和史航课题组合作宣布他们发现中心体的锚定调控神经前体细胞特性和大脑皮层的形成。2020年3月25日,国际学术期刊《自然》在线发表了这一成果。

研究人员在小鼠中发现将中心体锚定到顶膜可控制大脑皮层放射状神经胶质祖细胞(RGPs)的机械性能,从而控制其有丝分裂行为以及大脑皮层的大小和形成。RGP的母源中心体发育产生远端附件,将其锚定在顶膜上。选择性敲除中心体蛋白83(CEP83)消除了这些远端附件,并破坏了中心体在顶膜的锚定,导致微管紊乱以及顶膜的拉伸和变硬。CEP83的敲除还激活了yes-相关蛋白(YAP),并促进了RGP的过度增殖,以及随后间期祖细胞过度增殖,这导致了皮层形成异常折叠的扩大。同时,敲除YAP抑制了由CEP83缺失引起的皮质增大和折叠。总之,这些结果表明中心体在调节神经祖细胞的机械特征以及哺乳动物大脑皮层的大小和构型方面未知的功能。

据了解,RGPs是主要的神经祖细胞,它们在哺乳动物大脑皮层的发育中产生神经元和神经胶质。在RGP中,中心体位于远离大脑皮层心室区顶表面核的位置。但是,中心体这种独特亚细胞组织的分子基础和精确功能是未知的。

附:英文原文

Title: Centrosome anchoring regulates progenitor properties and cortical formation

Author: Wei Shao, Jiajun Yang, Ming He, Xiang-Yu Yu, Choong Heon Lee, Zhaohui Yang, Alexandra L. Joyner, Kathryn V. Anderson, Jiangyang Zhang, Meng-Fu Bryan Tsou, Hang Shi, Song-Hai Shi

Issue&Volume: 2020-03-25

Abstract: Radial glial progenitor cells (RGPs) are the major neural progenitor cells that generate neurons and glia in the developing mammalian cerebral cortex1,2,3,4. In RGPs, the centrosome is positioned away from the nucleus at the apical surface of the ventricular zone of the cerebral cortex5,6,7,8. However, the molecular basis and precise function of this distinctive subcellular organization of the centrosome are largely unknown. Here we show in mice that anchoring of the centrosome to the apical membrane controls the mechanical properties of cortical RGPs, and consequently their mitotic behaviour and the size and formation of the cortex. The mother centriole in RGPs develops distal appendages that anchor it to the apical membrane. Selective removal of centrosomal protein 83 (CEP83) eliminates these distal appendages and disrupts the anchorage of the centrosome to the apical membrane, resulting in the disorganization of microtubules and stretching and stiffening of the apical membrane. The elimination of CEP83 also activates the mechanically sensitive yes-associated protein (YAP) and promotes the excessive proliferation of RGPs, together with a subsequent overproduction of intermediate progenitor cells, which leads to the formation of an enlarged cortex with abnormal folding. Simultaneous elimination of YAP suppresses the cortical enlargement and folding that is induced by the removal of CEP83. Together, these results indicate a previously unknown role of the centrosome in regulating the mechanical features of neural progenitor cells and the size and configuration of the mammalian cerebral cortex.

DOI: 10.1038/s41586-020-2139-6

Source: https://www.nature.com/articles/s41586-020-2139-6

期刊信息

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html