4.8 Article

Coupling between hydrodynamic forces and planar cell polarity orients mammalian motile cilia

Journal

NATURE CELL BIOLOGY
Volume 12, Issue 4, Pages 341-U86

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/ncb2040

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Funding

  1. Agence Nationale de la Recherche
  2. International Human Frontier Science Program Organization
  3. Fondation NRJ-Institut de France
  4. Mairie de Paris start-up Grant
  5. Fondation pour la Recherche Medicale
  6. AXA Research Funds

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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.

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