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Centrosome anchoring regulates progenitor properties and cortical formation
Nature ( IF 64.8 ) Pub Date : 2020-03-25 , DOI: 10.1038/s41586-020-2139-6
Wei Shao 1, 2 , Jiajun Yang 3 , Ming He 3, 4 , Xiang-Yu Yu 3 , Choong Heon Lee 5 , Zhaohui Yang 1, 2 , Alexandra L Joyner 1, 2 , Kathryn V Anderson 1, 2 , Jiangyang Zhang 5 , Meng-Fu Bryan Tsou 2, 6 , Hang Shi 7 , Song-Hai Shi 1, 2, 3
Affiliation  

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.



中文翻译:

中心体锚定调节祖细胞特性和皮质形成

放射状胶质祖细胞 (RGP) 是在发育中的哺乳动物大脑皮层1,2,3,4中产生神经元和胶质细胞的主要神经祖细胞。在 RGP 中,中心体位于大脑皮层心室区顶端表面远离细胞核的位置5,6,7,8. 然而,中心体这种独特的亚细胞组织的分子基础和精确功能在很大程度上是未知的。在这里,我们在小鼠中显示,中心体锚定到顶膜控制皮质 RGP 的机械特性,从而控制它们的有丝分裂行为以及皮质的大小和形成。RGP 中的母体中心粒发育出远端附属物,将其锚定在顶膜上。选择性去除中心体蛋白 83 (CEP83) 消除了这些远端附属物并破坏了中心体与顶膜的锚定,导致微管的解体以及顶膜的拉伸和硬化。CEP83的消除也会激活机械敏感的yes相关蛋白(YAP)并促进RGPs的过度增殖,加上随后中间祖细胞的过度产生,导致形成具有异常折叠的扩大皮层。同时消除 YAP 可抑制由去除 CEP83 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配置方面具有以前未知的作用。

更新日期:2020-03-25
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