Non-canonical Wnt signaling regulates junctional mechanocoupling during angiogenic collective cell migration

Morphogenesis of hierarchical vascular networks depends on the integration of multiple biomechanical signals by endothelial cells, the cells lining the interior of blood vessels. Expansion of vascular networks arises through sprouting angiogenesis, a process involving extensive cell rearrangements a...

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Bibliographic Details
Published in:eLife 2019-06, Vol.8
Main Authors: Carvalho, Joana R, Fortunato, Isabela C, Fonseca, Catarina G, Pezzarossa, Anna, Barbacena, Pedro, Dominguez-Cejudo, Maria A, Vasconcelos, Francisca F, Santos, Nuno C, Carvalho, Filomena A, Franco, Claudio A
Format: Article
Language:English
Subjects:
Actin
Adherens junctions
alpha Catenin - metabolism
Angiogenesis
Animals
Behavior
Blood vessels
cdc42 GTP-Binding Protein - metabolism
Cdc42 protein
Cell adhesion & migration
Cell Biology
Cell junctions
Cell migration
Cell Movement
collective cell migration
Cytoskeleton
Developmental Biology
Endothelial cells
Endothelial Cells - physiology
Endothelium
Experiments
Histograms
House mouse
Ligands
mechanotransduction
Mice
Morphogenesis
Muscle proteins
Neovascularization
Neovascularization, Physiologic
non-canonical Wnt signaling
Observations
Physiological aspects
Polarity
Protein Binding
Statistical analysis
Vinculin
Vinculin - metabolism
Wnt protein
Wnt proteins
Wnt Signaling Pathway
Wnt-5a Protein - metabolism
α-catenin
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Summary:Morphogenesis of hierarchical vascular networks depends on the integration of multiple biomechanical signals by endothelial cells, the cells lining the interior of blood vessels. Expansion of vascular networks arises through sprouting angiogenesis, a process involving extensive cell rearrangements and collective cell migration. Yet, the mechanisms controlling angiogenic collective behavior remain poorly understood. Here, we show this collective cell behavior is regulated by non-canonical Wnt signaling. We identify that Wnt5a specifically activates Cdc42 at cell junctions downstream of ROR2 to reinforce coupling between adherens junctions and the actin cytoskeleton. We show that Wnt5a signaling stabilizes vinculin binding to alpha-catenin, and abrogation of vinculin in vivo and in vitro leads to uncoordinated polarity and deficient sprouting angiogenesis in . Our findings highlight how non-canonical Wnt signaling coordinates collective cell behavior during vascular morphogenesis by fine-tuning junctional mechanocoupling between endothelial cells.
ISSN:2050-084X
2050-084X
DOI:10.7554/elife.45853