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Title: Non-canonical Wnt signalling modulates the endothelial shear stress flow sensor in vascular remodelling
Authors: Franco, Claudio A ×
Jones, Martin L
Bernabeu, Miguel O
Vion, Anne-Clemence
Barbacena, Pedro
Fan, Jieqing
Mathivet, Thomas
Fonseca, Catarina G
Ragab, Anan
Yamaguchi, Terry P
Coveney, Peter V
Lang, Richard A
Gerhardt, Holger #
Issue Date: 4-Feb-2016
Publisher: eLife Sciences
Series Title: Elife vol:5
Article number: e07727
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.
URI: 
ISSN: 2050-084X
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Vascular Patterning Laboratory (VIB-KU Leuven Centre for Cancer Biology) (+)
× corresponding author
# (joint) last author

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