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Non-canonical Wnt signalling modulates the endothelial shear stress flow sensor in vascular remodelling

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Item Type:Article
Title:Non-canonical Wnt signalling modulates the endothelial shear stress flow sensor in vascular remodelling
Creators Name:Franco, C.A. and Jones, M.L. and Bernabeu, M.O. and Vion, A.C. and Barbacena, P. and Fan, J. and Mathivet, T. and Fonseca, C.G. and Ragab, A. and Yamaguchi, T.P. and Coveney, P.V. and Lang, R.A. and Gerhardt, H.
Abstract:Endothelial cells respond to molecular and physical forces in development and vascular homeostasis. Deregulation of endothelial responses to flow-induced shear is believed to contribute to many aspects of cardiovascular diseases including atherosclerosis. However, how molecular signals and shear-mediated physical forces integrate to regulate vascular patterning is poorly understood. Here we show that endothelial non-canonical Wnt signalling regulates endothelial sensitivity to shear forces. Loss of Wnt5a/Wnt11 renders endothelial cells more sensitive to shear, resulting in axial polarization and migration against flow at lower shear levels. Integration of flow modelling and polarity analysis in entire vascular networks demonstrates that polarization against flow is achieved differentially in artery, vein, capillaries and the primitive sprouting front. Collectively our data suggest that non-canonical Wnt signalling stabilizes forming vascular networks by reducing endothelial shear sensitivity, thus keeping vessels open under low flow conditions that prevail in the primitive plexus.
Keywords:Cell Line, Cell Movement, Cell Polarity, Endothelial Cells, Gene Expression Regulation, Mechanical Stress, Vascular Remodeling, Wnt Signaling Pathway, Animals, Mice
Publisher:eLife Sciences Publications
Page Range:e07727
Date:4 February 2016
Official Publication:https://doi.org/10.7554/eLife.07727
PubMed:View item in PubMed

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