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

First Author  Franco CA Year  2016
Journal  Elife Volume  5
Pages  e07727 PubMed ID  26845523
Mgi Jnum  J:230715 Mgi Id  MGI:5763672
Doi  10.7554/eLife.07727 Citation  Franco CA, et al. (2016) Non-canonical Wnt signalling modulates the endothelial shear stress flow sensor in vascular remodelling. Elife 5:e07727
abstractText  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.
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