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

Document Type

Article

Abstract

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.

Medical Subject Headings

Animals; Cell Polarity; Cells, Cultured; Cerebrospinal Fluid (metabolism); Cilia (metabolism); Ependyma (cytology, embryology, metabolism); Feedback, Physiological; Humans; Kinesins (metabolism); Mechanotransduction, Cellular; Mice; Mice, Transgenic; Morphogenesis; Motion; Mutation; Nerve Tissue Proteins (genetics, metabolism); Recombinant Fusion Proteins (metabolism); Stress, Mechanical; Time Factors; Transfection; Tumor Suppressor Proteins (metabolism)

Publication Date

4-1-2010

Publication Title

Nature cell biology

E-ISSN

1476-4679

Volume

12

Issue

4

First Page

341

Last Page

50

PubMed ID

20305650

Digital Object Identifier (DOI)

10.1038/ncb2040

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