Endothelial Cilia Mediate Low Flow Sensing during Zebrafish Vascular Development

• 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

SummaryThe 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.Video Abstract To view the video inline, enable JavaScript on your browser. However, you can download and view the video by clicking on the icon belowHelp with MP4 filesOptionsDownload video (70168 K)

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