The small GTPase Rac1 regulates auditory hair cell morphogenesis.
The small GTPase Rac1 regulates auditory hair cell morphogenesis.
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DOI：
10.1523/jneurosci.3998-09.2009
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发表时间：
2009-12-16
期刊：
影响因子：
--
通讯作者：
Lu X
中科院分区：
文献类型：
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作者：
Grimsley-Myers CM;Sipe CW;Géléoc GS;Lu X
感觉毛细胞的形态发生，特别是它们的机械转导细胞器，静纤毛束，需要肌动蛋白细胞骨架的高度组织化的重塑。Rho家族小GTP酶在这一过程中的作用仍不清楚。在这里，我们表明，删除Rac 1在耳上皮导致耳蜗上皮形态发生严重缺陷。突变耳蜗严重缩短，听毛细胞数量减少，听觉感觉上皮细胞结构异常。Rac 1突变体毛细胞也显示出平面细胞极性和静纤毛束形态发生的缺陷，包括束碎片或变形，以及动纤毛的错位或缺失。我们进一步证明了Rac-PAK信号通路介导动纤毛-静纤毛相互作用，并且是静纤毛束凝聚所必需的。总之，这些结果揭示了Rac 1在听觉感觉上皮和静纤毛束的形态发生中的关键功能。
Morphogenesis of sensory hair cells, in particular their mechanotransduction organelle, the stereociliary bundle, requires highly organized remodeling of the actin cytoskeleton. The roles of Rho family small GTPases during this process remain unknown. Here we show that deletion of Rac1 in the otic epithelium resulted in severe defects in cochlear epithelial morphogenesis. The mutant cochlea was severely shortened with a reduced number of auditory hair cells and cellular organization of the auditory sensory epithelium was abnormal. Rac1 mutant hair cells also displayed defects in planar cell polarity and morphogenesis of the stereociliary bundle, including bundle fragmentation or deformation, and mispositioning or absence of the kinocilium. We further demonstrate that a Rac-PAK signaling pathway mediates kinocilium-stereocilia interactions and is required for cohesion of the stereociliary bundle. Together, these results reveal a critical function of Rac1 in morphogenesis of the auditory sensory epithelium and stereociliary bundle.