Competition for endothelial cell polarity drives vascular morphogenesis in the mouse retina

Pedro Barbacena, Maria Dominguez-Cejudo, Catarina G. Fonseca, Manuel Gómez-González, Laura M. Faure, Georgia Zarkada, Andreia Pena, Anna Pezzarossa, Daniela Ramalho, Ylenia Giarratano, Marie Ouarné, David Barata, Isabela C. Fortunato, Lenka Henao Misikova, Ian Mauldin, Yulia Carvalho, Xavier Trepat, Pere Roca-Cusachs, Anne Eichmann, Miguel O. BernabeuCláudio A. Franco*

*Autor correspondente para este trabalho

Resultado de pesquisarevisão de pares

11 Transferências (Pure)

Resumo

Blood-vessel formation generates unique vascular patterns in each individual. The principles governing the apparent stochasticity of this process remain to be elucidated. Using mathematical methods, we find that the transition between two fundamental vascular morphogenetic programs—sprouting angiogenesis and vascular remodeling—is established by a shift of collective front-to-rear polarity of endothelial cells in the mouse retina. We demonstrate that the competition between biochemical (VEGFA) and mechanical (blood-flow-induced shear stress) cues controls this collective polarity shift. Shear stress increases tension at focal adhesions overriding VEGFA-driven collective polarization, which relies on tension at adherens junctions. We propose that vascular morphogenetic cues compete to regulate individual cell polarity and migration through tension shifts that translates into tissue-level emergent behaviors, ultimately leading to uniquely organized vascular patterns.

Idioma originalEnglish
Páginas (de-até)2321-2333.e9
Número de páginas23
RevistaDevelopmental Cell
Volume57
Número de emissão19
DOIs
Estado da publicaçãoPublicado - 10 out 2022

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