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

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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.
Original languageEnglish
Pages (from-to)2321-2333.e9
JournalDevelopmental Cell
Issue number19
Early online date10 Oct 2022
Publication statusPublished - 10 Oct 2022

Keywords / Materials (for Non-textual outputs)

  • Adherens Junctions/metabolism
  • Animals
  • Cell Movement/physiology
  • Cell Polarity/physiology
  • Endothelial Cells/metabolism
  • Mice
  • Morphogenesis
  • Retina/metabolism


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