Autor(es): Carvalho, Joana R. ; Fortunato, Isabela C. ; Fonseca, Catarina ; Pezzarossa, Anna ; Barbacena, Pedro ; Dominguez-Cejudo, Maria Angeles ; Vasconcelos, Francisca ; Santos, Nuno C. ; Carvalho, Filomena Almeida ; Franco, Claudio
Data: 2019
Identificador Persistente: http://hdl.handle.net/10451/48132
Origem: Repositório da Universidade de Lisboa
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 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.
