Department of Biomedical Sciences, Chonnam National University Medical School, Hwasun, 58128, Republic of Korea.
Center for Creative Biomedical Scientists at Chonnam National University, Hwasun, 58128, Republic of Korea.
Nat Commun. 2020 Apr 20;11(1):1860. doi: 10.1038/s41467-020-15248-2.
Ependymal cells (ECs) are multiciliated neuroepithelial cells that line the ventricles of the brain and the central canal of the spinal cord (SC). How ependymal motile cilia are maintained remains largely unexplored. Here we show that zebrafish embryos deficient in Wnt signaling have defective motile cilia, yet harbor intact basal bodies. With respect to maintenance of ependymal motile cilia, plcδ3a is a target gene of Wnt signaling. Lack of Connexin43 (Cx43), especially its channel function, decreases motile cilia and intercellular Ca wave (ICW) propagation. Genetic ablation of cx43 in zebrafish and mice diminished motile cilia. Finally, Cx43 is also expressed in ECs of the human SC. Taken together, our findings indicate that gap junction mediated ICWs play an important role in the maintenance of ependymal motile cilia, and suggest that the enhancement of functional gap junctions by pharmacological or genetic manipulations may be adopted to ameliorate motile ciliopathy.
室管膜细胞 (ECs) 是一种多纤毛的神经上皮细胞，排列在大脑脑室和脊髓中央管 (SC) 中。室管膜的运动纤毛是如何维持的仍然在很大程度上未被探索。在这里，我们发现缺乏 Wnt 信号的斑马鱼胚胎有缺陷的运动纤毛，但仍具有完整的基体。就维持室管膜运动纤毛而言，plcδ3a 是 Wnt 信号的靶基因。Connexin43 (Cx43) 的缺失，特别是其通道功能的缺失，会减少运动纤毛和细胞间 Ca 波 (ICW) 的传播。斑马鱼和小鼠中 cx43 的基因缺失会减少运动纤毛。最后，Cx43 也在人类 SC 的 ECs 中表达。总之，我们的发现表明缝隙连接介导的 ICWs 在维持室管膜运动纤毛方面发挥着重要作用，并表明通过药理学或遗传学手段增强功能性缝隙连接可能被用于改善运动纤毛病。
