Vascular Biology Laboratory, Lincoln's Inn Laboratories, London Research Institute, The Francis Crick Institute, London, United Kingdom; Instituto de Medicina Molecular, Faculdade de Medicina Universidade de Lisboa, Lisbon, Portugal
Vascular Biology Laboratory, Lincoln's Inn Laboratories, London Research Institute, The Francis Crick Institute, London, United Kingdom
Miguel O Bernabeu
Centre for Medical Informatics, Usher Institute, The University of Edinburgh, Edinburgh, United Kingdom; Centre for Computational Science, Department of Chemistry, University College London, London, United Kingdom
Anne-Clemence Vion
Vascular Biology Laboratory, Lincoln's Inn Laboratories, London Research Institute, The Francis Crick Institute, London, United Kingdom; Max-Delbrück-Center for Molecular Medicine, Berlin, Germany
Pedro Barbacena
Instituto de Medicina Molecular, Faculdade de Medicina Universidade de Lisboa, Lisbon, Portugal
Jieqing Fan
The Visual Systems Group, Division of Pediatric Ophthalmology, Cincinnati Children's Hospital Medical Center, Cincinnati, United States
Thomas Mathivet
Vascular Patterning Laboratory, Vesalius Research Center, Leuven, Belgium; Department of Oncology, Vascular Patterning Laboratory, Vesalius Research Center, Leuven, Belgium
Catarina G Fonseca
Instituto de Medicina Molecular, Faculdade de Medicina Universidade de Lisboa, Lisbon, Portugal
Anan Ragab
Vascular Biology Laboratory, Lincoln's Inn Laboratories, London Research Institute, The Francis Crick Institute, London, United Kingdom
Terry P Yamaguchi
Cancer and Developmental Biology Laboratory, Center for Cancer Research, NCI-Frederick, National Institutes of Health, Frederick, United States
Peter V Coveney
Centre for Computational Science, Department of Chemistry, University College London, London, United Kingdom
Richard A Lang
The Visual Systems Group, Division of Pediatric Ophthalmology, Cincinnati Children's Hospital Medical Center, Cincinnati, United States
Vascular Biology Laboratory, Lincoln's Inn Laboratories, London Research Institute, The Francis Crick Institute, London, United Kingdom; Max-Delbrück-Center for Molecular Medicine, Berlin, Germany; Vascular Patterning Laboratory, Vesalius Research Center, Leuven, Belgium; Department of Oncology, Vascular Patterning Laboratory, Vesalius Research Center, Leuven, Belgium; German Center for Cardiovascular Research, Berlin, Germany; Berlin Institute of Health, Berlin, Germany
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.
