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Cell Rep. 2014 Mar 13;6(5):799-808. doi: 10.1016/j.celrep.2014.01.032. Epub 2014 Feb 20.

Endothelial cilia mediate low flow sensing during zebrafish vascular development.

Author information

1
Institut de Génétique et de Biologie Moléculaire et Cellulaire, 67400 Illkirch, France; Centre National de la Recherche Scientifique, UMR7104, 67404 Illkirch, France; Institut National de la Santé et de la Recherche Médicale, U964, 67404 Illkirch, France; Université de Strasbourg, 67404 Illkirch, France.
2
Department of Electrical and Computer Engineering, University of California, Santa Barbara, Santa Barbara, CA 93106, USA.
3
Institut du Cerveau et de la Moelle Épinière (ICM), Hôpital de la Pitié-Salpêtrière, 75013 Paris, France; Inserm UMRS 1127, 75013 Paris, France; CNRS UMR 7225, 75013 Paris, France; UPMC University of Paris 06, 75005 Paris, France.
4
Electron Microscopy Core Facility, Cell Biology and Biophysics Unit, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
5
Institut de Génétique et de Biologie Moléculaire et Cellulaire, 67400 Illkirch, France; Centre National de la Recherche Scientifique, UMR7104, 67404 Illkirch, France; Institut National de la Santé et de la Recherche Médicale, U964, 67404 Illkirch, France; Université de Strasbourg, 67404 Illkirch, France. Electronic address: julien@igbmc.fr.

Abstract

The pattern of blood flow has long been thought to play a significant role in vascular morphogenesis, yet the flow-sensing mechanism that is involved at early embryonic stages, when flow forces are low, remains unclear. It has been proposed that endothelial cells use primary cilia to sense flow, but this has never been tested in vivo. Here we show, by noninvasive, high-resolution imaging of live zebrafish embryos, that endothelial cilia progressively deflect at the onset of blood flow and that the deflection angle correlates with calcium levels in endothelial cells. We demonstrate that alterations in shear stress, ciliogenesis, or expression of the calcium channel PKD2 impair the endothelial calcium level and both increase and perturb vascular morphogenesis. Altogether, these results demonstrate that endothelial cilia constitute a highly sensitive structure that permits the detection of low shear forces during vascular morphogenesis.

PMID:
24561257
DOI:
10.1016/j.celrep.2014.01.032
[Indexed for MEDLINE]
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