Failure of centrosome migration causes a loss of motile cilia in talpid 3 mutants
Failure of centrosome migration causes a loss of motile cilia in talpid 3 mutants
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中心体迁移失败导致 talpid 3 突变体活动纤毛丧失
DOI：
10.1002/dvdy.24012
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发表时间：
2013
影响因子：
2.5
通讯作者：
Stephen L
中科院分区：
文献类型：
--
作者：
Stephen L
研究背景中心体蛋白TALPID 3（KIAA 0586）的功能缺失突变导致动物模型中初级纤毛形成失败，并与Hedgehog信号传导缺陷相关。然而，目前还不清楚TALPID 3是否仅是初级纤毛形成所必需的，或者它是否是所有纤毛发生所必需的，包括多纤毛细胞中运动纤毛的发生。结果FOXJ 1是多纤毛细胞命运的关键调节因子，在20 HH期鸡前脑和后脑的背神经外胚层中表达，前脑脉络丛的室管膜细胞随后在29小时从显示单个短纤毛转变为显示多个长运动纤毛（E8）。初级纤毛和长运动纤毛在室管膜细胞上很少见到。电子显微镜观察发现，TALPID 3室管膜细胞中存在着与FOXJ 1表达相一致的多个中心体，但这些中心体不能迁移到室管膜细胞的顶面，尽管轴丝的形成有时会被抑制。结论TALPID 3通常位于近端中心体，在纤毛发生之前，它是中心体迁移所必需的，但并不是从头中心体发生，多纤毛命运，发育动力学242：923-931，2013。© 2013 Wiley Periodicals，Inc.
BackgroundLoss of function mutations in the centrosomal protein TALPID3 (KIAA0586) cause a failure of primary cilia formation in animal models and are associated with defective Hedgehog signalling. It is unclear, however, if TALPID3 is required only for primary cilia formation or if it is essential for all ciliogenesis, including that of motile cilia in multiciliate cells.ResultsFOXJ1, a key regulator of multiciliate cell fate, is expressed in the dorsal neuroectoderm of the chicken forebrain and hindbrain at stage 20HH, in areas that will give rise to choroid plexuses in bothwtandtalpid3embryos.Wtependymal cells of the prosencephalic choroid plexuses subsequently transition from exhibiting single short cilia to multiple long motile cilia at 29HH (E8). Primary cilia and long motile cilia were only rarely observed ontalpid3ependymal cells. Electron microscopy determined thattalpid3ependymal cells do develop multiple centrosomes in accordance withFOXJ1expression, but these fail to migrate to the apical surface of ependymal cells although axoneme formation was sometimes observed.ConclusionsTALPID3, which normally localises to the proximal centrosome, is essential for centrosomal migration prior to ciliogenesis but is not directly required for de novo centriologenesis, multiciliated fate, or axoneme formation.Developmental Dynamics 242:923–931, 2013. © 2013 Wiley Periodicals, Inc.