Vangl2 directs the posterior tilting and asymmetric localization of motile primary cilia
Vangl2 directs the posterior tilting and asymmetric localization of motile primary cilia
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DOI：
10.1038/ncb2042
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发表时间：
2010-04-01
影响因子：
21.3
通讯作者：
Ciruna, Brian
中科院分区：
文献类型：
--
作者：
Borovina, Antonia;Superina, Simone;Ciruna, Brian
纤毛是基于微管的细胞器，其投射到细胞外空间，在环境线索的感知和整合中起作用（1），并调节Hedgehog信号转导（2）。睫状体缺陷与多种多样的人类疾病（3，4）的紧急关联促进了对纤毛发生的分子遗传调控的研究。尽管最近的研究表明纤毛形成中存在平面细胞极性（PCP），但这一结论是基于对PCP信号转导的非特异性蛋白质或下游效应物的分析（5-10）。在这里，我们表征了缺乏所有Vangl 2功能的斑马鱼胚胎（11），Vangl 2功能是PCP信号传导途径的核心和特定组分。使用Arl 13 b-GFP作为纤毛轴丝的活标记物，我们证明Vangl 2不是纤毛发生所需的。相反，Vangl 2控制着排列在神经腔、库普弗囊泡和前肾管中的初级运动纤毛的向后倾斜。此外，我们表明，Vangl 2是所需的不对称本地化的纤毛后顶膜的神经上皮细胞。我们的研究结果表明PCP在运动的初级纤毛的不对称定位和定向，建立正常胚胎发育中涉及的定向流动，
Cilia are microtubule-based organelles that project into the extracellular space, function in the perception and integration of environmental cues(1), and regulate Hedgehog signal transduction(2). The emergent association of ciliary defects with diverse and pleiotropic human disorders(3,4) has fuelled investigation into the molecular genetic regulation of ciliogenesis. Although recent studies implicate planar cell polarity (PCP) in cilia formation, this conclusion is based on analyses of proteins that are not specific to, or downstream effectors of PCP signal transduction(5-10). Here we characterize zebrafish embryos devoid of all Vangl2 function(11), a core and specific component of the PCP signalling pathway. Using Arl13b-GFP as a live marker of the ciliary axoneme, we demonstrate that Vangl2 is not required for ciliogenesis. Instead, Vangl2 controls the posterior tilting of primary motile cilia lining the neurocoel, Kupffer's vesicle and pronephric duct. Furthermore, we show that Vangl2 is required for asymmetric localization of cilia to the posterior apical membrane of neuroepithelial cells. Our results indicate a and essential role for PCP in the asymmetric localization and orientation of motile primary cilia, establishing directional flow implicated in normal embryonic development and