CAMSAP3 is required for mTORC1-dependent ependymal cell growth and lateral ventricle shaping in mouse brains
CAMSAP3 is required for mTORC1-dependent ependymal cell growth and lateral ventricle shaping in mouse brains
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DOI：
10.1242/dev.195073
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发表时间：
2021-02-01
期刊：
影响因子：
4.6
通讯作者：
Takeichi, Masatoshi
中科院分区：
文献类型：
--
作者：
Kimura, Toshiya;Saito, Hiroko;Takeichi, Masatoshi
微管（MT）调节许多细胞过程，但其在脑形态发生中的作用还不清楚。这里.我们发现CAMSAP 3，一种非中心体微管调节因子，对侧脑室的形成很重要。在室管膜细胞分化过程中，CAMSAP 3集中在顶端结构域，在这些部位产生MT网络。Camsap3突变小鼠表现出异常狭窄的侧脑室，其中过度狭窄或融合被诱导，导致脑室和脑室下区的神经干细胞减少。这种缺陷至少部分归因于新皮质室管膜细胞未能扩大其顶端域，这是扩大心室腔所必需的过程。mTORC1是室管膜细胞生长所必需的，但其活性在突变细胞中下调。介导mTORC 1活化的溶酶体在突变细胞的顶端区域倾向于减少，沿着在相应位点的顶端MT网络紊乱。这些发现表明，CAMSAP 3支持mTORC 1信号传导所需的室管膜细胞生长通过MT网络调节，并反过来，侧脑室的塑造。
Microtubules (MTs) regulate numerous cellular processes, but their roles in brain morphogenesis are not well known. Here. we show that CAMSAP3, a non-centrosomal microtubule regulator, is important for shaping the lateral ventricles. In differentiating ependymal cells, CAMSAP3 became concentrated at the apical domains, serving to generate MT networks at these sites. Camsap3-mutated mice showed abnormally narrow lateral ventricles, in which excessive stenosis or fusion was induced, leading to a decrease of neural stem cells at the ventricular and subventricular zones. This defect was ascribed at least in part to a failure of neocortical ependymal cells to broaden their apical domain, a process necessary for expanding the ventricular cavities. mTORC1 was required for ependymal cell growth but its activity was downregulated in mutant cells. Lysosomes, which mediate mTORC1 activation, tended to be reduced at the apical regions of the mutant cells, along with disorganized apical MT networks at the corresponding sites. These findings suggest that CAMSAP3 supports mTORC1 signaling required for ependymal cell growth via MT network regulation, and, in turn, shaping of the lateral ventricles.