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Blood flow drives lumen formation by inverse membrane blebbing during angiogenesis in vivo

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Item Type:Article
Title:Blood flow drives lumen formation by inverse membrane blebbing during angiogenesis in vivo
Creators Name:Gebala, V. and Collins, R. and Geudens, I. and Phng, L.K. and Gerhardt, H.
Abstract:How vascular tubes build, maintain and adapt continuously perfused lumens to meet local metabolic needs remains poorly understood. Recent studies showed that blood flow itself plays a critical role in the remodelling of vascular networks, and suggested it is also required for the lumenization of new vascular connections. However, it is still unknown how haemodynamic forces contribute to the formation of new vascular lumens during blood vessel morphogenesis. Here we report that blood flow drives lumen expansion during sprouting angiogenesis in vivo by inducing spherical deformations of the apical membrane of endothelial cells, in a process that we have termed inverse blebbing. We show that endothelial cells react to these membrane intrusions by local and transient recruitment and contraction of actomyosin, and that this mechanism is required for single, unidirectional lumen expansion in angiogenic sprouts. Our work identifies inverse membrane blebbing as a cellular response to high external pressure. We show that in the case of blood vessels such membrane dynamics can drive local cell shape changes required for global tissue morphogenesis, shedding light on a pressure-driven mechanism of lumen formation in vertebrates.
Keywords:Actomyosin, Blood Vessels, Confocal Microscopy, Endothelial Cells, Genetically Modified Animals, Inbred C57BL Mice, Luminescent Proteins, Morphogenesis, Physiologic Neovascularization, Regional Blood Flow, Time-Lapse Imaging, Transgenic Mice, Animals, Mice, Zebrafish
Source:Nature Cell Biology
Publisher:Nature Publishing Group
Page Range:443-450
Date:April 2016
Official Publication:https://doi.org/10.1038/ncb3320
PubMed:View item in PubMed

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