Non-canonical Wnt signaling regulates junctional mechanocoupling during angiogenic collective cell migration
- Universidade de Lisboa, Portugal
Abstract
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 behaviour 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 Mus musculus. Our findings highlight how non-canonical Wnt signaling coordinates collective cell behavior during vascular morphogenesis by fine-tuning junctional mechanocoupling between endothelial cells.
Data availability
All data generated or analyzed during this study are included in the manuscript and supporting files.
Article and author information
Author details
Francisca F Vasconcelos
Funding
H2020 European Research Council (679368)
- Claudio A Franco
Fundação para a Ciência e a Tecnologia (IF/00412/2012/CP0163/CT0007)
- Claudio A Franco
Fondation Leducq (17CVD03)
- Claudio A Franco
H2020 Spreading Excellence and Widening Participation (692322)
- Claudio A Franco
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: Mice were maintained at the Instituto de Medicina Molecular (iMM) under standard husbandry conditions and under national regulations, under the license AWB_2015_11_CAF_Polaridade
Copyright
© 2019, Carvalho 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.
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Non-canonical Wnt signaling regulates junctional mechanocoupling during angiogenic collective cell migration
eLife 8:e45853.
https://doi.org/10.7554/eLife.45853
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