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Primary cilia sensitize endothelial cells to BMP and prevent excessive vascular regression

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Item Type:Article
Title:Primary cilia sensitize endothelial cells to BMP and prevent excessive vascular regression
Creators Name:Vion, A.C., Alt, S., Klaus-Bergmann, A., Szymborska, A., Zheng, T., Perovic, T., Hammoutene, A., Oliveira, M.B., Bartels-Klein, E., Hollfinger, I., Rautou, P.E., Bernabeu, M.O. and Gerhardt, H.
Abstract:Blood flow shapes vascular networks by orchestrating endothelial cell behavior and function. How endothelial cells read and interpret flow-derived signals is poorly understood. Here, we show that endothelial cells in the developing mouse retina form and use luminal primary cilia to stabilize vessel connections selectively in parts of the remodeling vascular plexus experiencing low and intermediate shear stress. Inducible genetic deletion of the essential cilia component intraflagellar transport protein 88 (IFT88) in endothelial cells caused premature and random vessel regression without affecting proliferation, cell cycle progression, or apoptosis. IFT88 mutant cells lacking primary cilia displayed reduced polarization against blood flow, selectively at low and intermediate flow levels, and have a stronger migratory behavior. Molecularly, we identify that primary cilia endow endothelial cells with strongly enhanced sensitivity to bone morphogenic protein 9 (BMP9), selectively under low flow. We propose that BMP9 signaling cooperates with the primary cilia at low flow to keep immature vessels open before high shear stress-mediated remodeling.
Keywords:Blood Vessels, Bone Morphogenetic Proteins, Cell Movement, Cell Polarity, Cilia, Nonmammalian Embryo, Endothelial Cells, Human Umbilical Vein Endothelial Cells, Inbred C57BL Mice, Knockout Mice, Mechanical Stress, Vascular Remodeling, Animals, Zebrafish
Source:Journal of Cell Biology
Publisher:Rockefeller University Press
Page Range:1651-1665
Date:7 May 2018
Additional Information:copyright © 2018 Vion et al.
Official Publication:https://doi.org/10.1083/jcb.201706151
PubMed:View item in PubMed

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