Non-canonical Wnt signalling modulates the endothelial shear stress flow sensor in vascular remodelling
- London Research Institute, United Kingdom
- The University of Edinburgh, United Kingdom
- Faculdade de Medicina Universidade de Lisboa, Portugal
- Cincinnati Children's Hospital Medical Center, United States
- Vesalius Research Center, Belgium
- National Institutes of Health, United States
- University College London, United Kingdom
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.
Article and author information
Author details
Ethics
Animal experimentation: Animal procedures were performed in accordance with the United Kingdom Home Office Animal Act 1986 under the authority of project license PPL 80/2391.
Copyright
© 2016, Franco et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 4,643
- views
-
- 1,404
- downloads
-
- 128
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Citations by DOI
-
- 128
- citations for umbrella DOI https://doi.org/10.7554/eLife.07727
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Non-canonical Wnt signalling modulates the endothelial shear stress flow sensor in vascular remodelling
eLife 5:e07727.
https://doi.org/10.7554/eLife.07727
