title: Non-canonical Wnt signalling modulates the endothelial shear stress flow sensor in vascular remodelling.
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.
authors: 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.
authors: Claudio A
authors: http://orcid.org/0000-0002-2861-3883
authors: CA
authors: Franco
authors: Vascular Biology Laboratory, Lincoln's Inn Laboratories, London Research Institute, The Francis Crick Institute, London, United Kingdom.
authors: Martin L
authors: http://orcid.org/0000-0003-0994-5652
authors: ML
authors: Jones
authors: 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.
authors: Miguel O
authors: MO
authors: Bernabeu
authors: 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.
authors: Anne-Clemence
authors: AC
authors: Vion
authors: Instituto de Medicina Molecular, Faculdade de Medicina Universidade de Lisboa, Lisbon, Portugal.
authors: Pedro
authors: P
authors: Barbacena
authors: The Visual Systems Group, Division of Pediatric Ophthalmology, Cincinnati Children's Hospital Medical Center, Cincinnati, United States.
authors: Jieqing
authors: J
authors: Fan
authors: Vascular Patterning Laboratory, Vesalius Research Center, Leuven, Belgium.|Department of Oncology, Vascular Patterning Laboratory, Vesalius Research Center, Leuven, Belgium.
authors: Thomas
authors: T
authors: Mathivet
authors: Instituto de Medicina Molecular, Faculdade de Medicina Universidade de Lisboa, Lisbon, Portugal.
authors: Catarina G
authors: CG
authors: Fonseca
authors: Vascular Biology Laboratory, Lincoln's Inn Laboratories, London Research Institute, The Francis Crick Institute, London, United Kingdom.
authors: Anan
authors: A
authors: Ragab
authors: Cancer and Developmental Biology Laboratory, Center for Cancer Research, NCI-Frederick, National Institutes of Health, Frederick, United States.
authors: Terry P
authors: TP
authors: Yamaguchi
authors: Centre for Computational Science, Department of Chemistry, University College London, London, United Kingdom.
authors: Peter V
authors: PV
authors: Coveney
authors: The Visual Systems Group, Division of Pediatric Ophthalmology, Cincinnati Children's Hospital Medical Center, Cincinnati, United States.
authors: Richard A
authors: RA
authors: Lang
authors: 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.
authors: Holger
authors: http://orcid.org/0000-0002-3030-0384
authors: H
authors: Gerhardt
mesh_terms: D000818:Animals; D002460:Cell Line; D002465:Cell Movement; D016764:Cell Polarity; D042783:Endothelial Cells / Q000502:physiology*; D005786:Gene Expression Regulation; D051379:Mice; D013314:Stress, Mechanical; D066253:Vascular Remodeling; D060449:Wnt Signaling Pathway
keywords: angiogenesis; cell biology; developmental biology; flow sensing; mouse; retinal vasculature; shear stress; stem cells; vessel regression