Daple Coordinates Planar Polarized Microtubule Dynamics in Ependymal Cells and Contributes to Hydrocephalus
Daple Coordinates Planar Polarized Microtubule Dynamics in Ependymal Cells and Contributes to Hydrocephalus
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DOI：
10.1016/j.celrep.2017.06.089
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发表时间：
2017-07-25
期刊：
影响因子：
8.8
通讯作者：
Takahashi, Masahide
中科院分区：
文献类型：
--
作者：
Takagishi, Maki;Sawada, Masato;Takahashi, Masahide
位于脑室的室管膜细胞中的活动纤毛表现出协调的跳动运动，驱动定向脑脊液（CSF）流动并引导神经母细胞迁移。在这些多纤毛细胞的顶皮层，平面细胞极性（PCP）蛋白的不对称定位是微管动力学平面极化所必需的，它协调纤毛方向。 Daple 是一种散乱的关联蛋白，控制非经典 Wnt 信号通路和细胞运动。在这里，我们发现 Daple 缺陷小鼠出现脑积水，并且它们的室管膜纤毛缺乏协调方向。 Daple 调节室管膜细胞前侧的微管动力学，进而定向脑脊液定向流动所需的纤毛基体。这些结果证明了 Daple 在运动纤毛平面极性中的重要作用，并为理解室管膜细胞平面极性的机制和功能提供了框架。
Motile cilia in ependymal cells, which line the cerebral ventricles, exhibit a coordinated beating motion that drives directional cerebrospinal fluid (CSF) flow and guides neuroblast migration. At the apical cortex of these multi-ciliated cells, asymmetric localization of planar cell polarity (PCP) proteins is required for the planar polarization of microtubule dynamics, which coordinates cilia orientation. Daple is a disheveledassociating protein that controls the non-canonical Wnt signaling pathway and cell motility. Here, we show that Daple-deficient mice present hydrocephalus and their ependymal cilia lack coordinated orientation. Daple regulates microtubule dynamics at the anterior side of ependymal cells, which in turn orients the cilial basal bodies required for the directional cerebrospinal fluid flow. These results demonstrate an important role for Daple in planar polarity in motile cilia and provide a framework for understanding the mechanisms and functions of planar polarization in the ependymal cells.