Endothelial Cilia Mediate Low Flow Sensing during Zebrafish Vascular Development

• Published in: Cell reports (Cambridge) Vol. 6; no. 5; pp. 799 - 808
• Main Authors: Goetz, Jacky G., Steed, Emily, Ferreira, Rita R., Roth, Stéphane, Ramspacher, Caroline, Boselli, Francesco, Charvin, Gilles, Liebling, Michael, Wyart, Claire, Schwab, Yannick, Vermot, Julien
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-03-2014; Elsevier
• Subjects: Animals; Cardiovascular System - embryology; Cells, Cultured; Cellular Biology; Cilia - physiology; Danio rerio; Embryo, Nonmammalian - blood supply; Embryonic Development; Endothelial Cells - cytology; Endothelial Cells - ultrastructure; Life Sciences; Neovascularization, Physiologic; Zebrafish - embryology
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2014.01.032

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.
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•Endothelial cilia are present during angiogenesis and deflected by low flow forces•Cilia deflection leads to endothelial calcium increase as flow forces increase•Endothelial cilia ultrastructure is unique, which makes it highly flexible•Cilia, flow, and PKD2 are necessary for early angiogenesis
Blood flow is a major mechanical stimulus that controls vascular development, yet the mechanodetection mechanisms that drive angiogenesis are poorly understood. Vermot and colleagues now show that primary cilia located at the endothelial cell surface regulate early angiogenesis. The authors demonstrate that cilia-mediated mechanodetection detects low flow forces through PKD2-mediated calcium fluxes.