TY - JOUR
T1 - Coupling between hydrodynamic forces and planar cell polarity orients mammalian motile cilia
AU - Guirao, Boris
AU - Meunier, Alice
AU - Mortaud, Stéphane
AU - Aguilar, Andrea
AU - Corsi, Jean Marc
AU - Strehl, Laetitia
AU - Hirota, Yuki
AU - Desoeuvre, Angélique
AU - Boutin, Camille
AU - Han, Young Goo
AU - Mirzadeh, Zaman
AU - Cremer, Harold
AU - Montcouquiol, Mireille
AU - Sawamoto, Kazunobu
AU - Spassky, Nathalie
N1 - Funding Information:
We thank A. Buguin, B. Lemaire and J.-H. Codarbox for their help with the flow set-up realization. We thank Marie-Paule Muriel for excellent technical assistance and for having shared her T.E.M. background. We thank the Pitié-Salpêtrière and Cochin hospitals imaging centres. We thank B. Yoder (University of Alabama, Birmingham) and L.S. Goldstein (University of California San Diego) for providing us with Ift88fl/fl and Kif3afl/KO mice, respectively. We thank A. Alvarez-Buylla for making Ift88fl/fl mice available. We thank M. Bornens for the gift of CTR453 antibody, X. Morin for the gift of pCX plasmid and MH. Bré for the gift of TAP antibody. We also thank M. Bornens, B. Durand, J.-F. Joanny and Y. Bellaïche for discussions and reading of this manuscript. This work was supported by grants from the Agence Nationale de la Recherche (to N.S.), The International Human Frontier Science Program Organization (to N.S. and K.S.), the Fondation NRJ-Institut de France (to N.S.), the Mairie de Paris start-up Grant (to N.S.), by Fondation pour la Recherche Médicale and AXA Research Funds fellowships to A.M. and Neuropole de Recherche Francilien fellowship to J.-M.C. B.G. and A.A. were fellows of the Ministère de l’enseignement supérieur et de la recherche.
PY - 2010/4
Y1 - 2010/4
N2 - 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.
AB - 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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U2 - 10.1038/ncb2040
DO - 10.1038/ncb2040
M3 - Article
C2 - 20305650
AN - SCOPUS:77950498085
SN - 1465-7392
VL - 12
SP - 341
EP - 350
JO - Nature Cell Biology
JF - Nature Cell Biology
IS - 4
ER -