State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China.
University of Chinese Academy of Sciences, Beijing, 100049, China.
Sci Rep. 2020 Jul 24;10(1):12435. doi: 10.1038/s41598-020-69447-4.
Hydrocephalus is a brain disorder triggered by cerebrospinal fluid accumulation in brain cavities. Even though cerebrospinal fluid flow is known to be driven by the orchestrated beating of the bundled motile cilia of ependymal cells, little is known about the mechanism of ciliary motility. RSPH9 is increasingly becoming recognized as a vital component of radial spokes in ciliary "9 + 2" ultrastructure organization. Here, we show that deletion of the Rsph9 gene leads to the development of hydrocephalus in the early postnatal period. However, the neurodevelopment and astrocyte development are normal in embryonic Rsph9 mice. The tubular structure of the central aqueduct was comparable in Rsph9 mice. Using high-speed video microscopy, we visualized lower beating amplitude and irregular rotation beating pattern of cilia bundles in Rsph9 mice compared with that of wild-type mice. And the centriolar patch size was significantly increased in Rsph9 cells. TEM results showed that deletion of Rsph9 causes little impact in ciliary axonemal organization but the Rsph9 cilia frequently had abnormal ectopic ciliary membrane inclusions. In addition, hydrocephalus in Rsph9 mice results in the development of astrogliosis, microgliosis and cerebrovascular abnormalities. Eventually, the ependymal cells sloughed off of the lateral wall. Our results collectively suggested that RSPH9 is essential for ciliary structure and motility of mouse ependymal cilia, and its deletion causes the pathogenesis of hydrocephalus.
脑积水是一种由脑腔中脑脊液积聚引起的脑部疾病。尽管已知脑脊液流动是由室管膜细胞的有节奏的纤毛运动所驱动，但对于纤毛运动的机制知之甚少。RSPH9 越来越被认为是纤毛“9+2”超微结构组织中放射辐条的重要组成部分。在这里，我们表明 Rsph9 基因缺失会导致幼鼠期后发生脑积水。然而，胚胎 Rsph9 小鼠的神经发育和星形胶质细胞发育正常。中央导水管的管状结构在 Rsph9 小鼠中是可比的。使用高速视频显微镜，我们观察到 Rsph9 小鼠的纤毛束的摆动幅度较低且旋转摆动模式不规则，与野生型小鼠相比。并且 Rsph9 细胞中的中心粒斑大小显著增加。TEM 结果表明，Rsph9 的缺失对纤毛轴丝的组织几乎没有影响，但 Rsph9 纤毛经常有异常的纤毛膜内包涵体。此外，Rsph9 小鼠的脑积水导致星形胶质细胞增生、小胶质细胞增生和脑血管异常。最终，室管膜细胞从侧壁脱落。我们的结果表明，RSPH9 对小鼠室管膜细胞的纤毛结构和运动至关重要，其缺失导致脑积水的发病机制。
