Cluap1 localizes preferentially to the base and tip of cilia and is required for ciliogenesis in the mouse embryo
Cluap1 localizes preferentially to the base and tip of cilia and is required for ciliogenesis in the mouse embryo
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DOI：
10.1016/j.ydbio.2013.05.024
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发表时间：
2013-09-01
影响因子：
2.7
通讯作者：
Hamada, Hiroshi
中科院分区：
文献类型：
--
作者：
Botilde, Yanick;Yoshibaa'b, Satoko;Hamada, Hiroshi
麒麟基因是斑马鱼中几个突变导致囊肾的基因之一。我们现在通过产生clap1敲除（clap1(-/-)）小鼠，研究了clap1的小鼠同源基因clap1在胚胎发育中的作用。clap1（-/-）胚胎在妊娠中期死亡，表现出包括淋巴结和神经管在内的各个区域的纤毛发育受损。在突变体中发现基体与细胞的顶膜正确对接，但轴突不能生长。Cluap1是一种纤毛蛋白，优先定位于纤毛的基部和尖端。通过Pacthed1-lacZ报告基因发现，刺猬信号在胚胎日(E) 8.5时丢失，但在胚胎日(E) 9.0时异位扩增。敲除Cluap1的胚胎也未能在侧板中表现出左右不对称的Nodal表达，这很可能是由于节点冠细胞中Hedgehog信号的缺失，从而导致这些细胞中Gdf1表达的明显下调。冠细胞特异性的clap1表达恢复恢复了突变胚冠细胞中Gdf1的表达和侧板中左侧淋巴结的表达。我们的研究结果表明，Cluap1通过调节纤毛基部和尖端的鞭毛内运输（IFT）周期来促进纤毛的发生。(C) 2013爱思唯尔公司版权所有。
Qilin is one of several genes in zebrafish whose mutation results in cystic kidney. We have now studied the role of its mouse ortholog, Cluap1, in embryonic development by generating Cluap1 knockout (Cluap1(-/-)) mice. Cluap1(-/-) embryos died mid-gestation manifesting impairment of ciliogenesis in various regions including the node and neural tube. The basal body was found to be properly docked to the apical membrane of cells in the mutant, but the axoneme failed to grow. Cluap1 is a ciliary protein and is preferentially localized at the base and tip of cilia. Hedgehog signaling, as revealed with a Pacthed1-lacZ reporter gene, was lost in Cluapri-embryos at embryonic day (E) 8.5 but was ectopically expanded at E9.0. The Cluap1 knockout embryos also failed to manifest left right asymmetric expression of Nodal in the lateral plate, most likely as a result of the loss of Hedgehog signaling in node crown cells that in turn leads to pronounced down-regulation of Gdf1 expression in these cells. Crown cell-specific restoration of Cluap1 expression rescued Gdf1 expression in crown cells and left-sided Nodal expression in the lateral plate of mutant embryos. Our results suggest that Cluap1 contributes to ciliogenesis by regulating the intraflagellar transport (IFT) cycle at the base and tip of the cilium. (C) 2013 Elsevier Inc. All rights reserved.