Coupling between hydrodynamic forces and planar cell polarity orients mammalian motile cilia
Coupling between hydrodynamic forces and planar cell polarity orients mammalian motile cilia
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DOI：
10.1038/ncb2040
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发表时间：
2010-04-01
影响因子：
21.3
通讯作者：
Spassky, Nathalie
中科院分区：
文献类型：
--
作者：
Guirao, Boris;Meunier, Alice;Spassky, Nathalie
在哺乳动物中，活动纤毛覆盖许多器官，如输卵管、呼吸道和脑室。这些器官的发育和功能关键取决于由纤毛跳动的对齐确保的有效的定向流体流动。为了确定在这个过程中所涉及的机制，我们分析了小鼠脑室运动纤毛，使用生物物理和分子方法。我们的研究结果突出了室管膜纤毛的原始定向机制，即基体首先与随机方向顶部对接，然后在有限的时间范围内通过水动力和平面细胞极性（PCP）蛋白Vangl2之间的耦合在一个共同的方向上重新定向。这确定了外部流体动力学线索和细胞内PCP信号之间的直接联系。我们的研究结果扩展了已知的PCP机制，整合水动力作为远程极性信号，主张室管膜纤毛可能的感觉作用，并将感兴趣的流体流动介导的形态发生的研究。
In mammals, motile cilia cover many organs, such as fallopian tubes, respiratory tracts and brain ventricles. The development and function of these organs critically depend on efficient directional fluid flow ensured by the alignment of ciliary beating. To identify the mechanisms involved in this process, we analysed motile cilia of mouse brain ventricles, using biophysical and molecular approaches. Our results highlight an original orientation mechanism for ependymal cilia whereby basal bodies first dock apically with random orientations, and then reorient in a common direction through a coupling between hydrodynamic forces and the planar cell polarity (PCP) protein Vangl2, within a limited time-frame. This identifies a direct link between external hydrodynamic cues and intracellular PCP signalling. Our findings extend known PCP mechanisms by integrating hydrodynamic forces as long-range polarity signals, argue for a possible sensory role of ependymal cilia, and will be of interest for the study of fluid flow-mediated morphogenesis.