@article{cd4e79799b41458d9057c210c45fe63c,
title = "Competition for endothelial cell polarity drives vascular morphogenesis in the mouse retina",
abstract = "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.",
keywords = "Adherens Junctions/metabolism, Animals, Cell Movement/physiology, Cell Polarity/physiology, Endothelial Cells/metabolism, Mice, Morphogenesis, Retina/metabolism",
author = "Pedro Barbacena and Maria Dominguez-Cejudo and Fonseca, {Catarina G} and Manuel Gomez-Gonzales and Faure, {Laura M} and Georgia Zarkada and Andreia Pena and Anna Pezzarossa and Daniela Ramalho and Ylenia Giarratano and {Marie Ouarn{\'e}}, Marie and David Barata and Isabela Fortunato and {Henao Misikova}, Lenka and Ian Mauldin and Yulia Carvalho and Xavier Trepat and Pere Roca-Cusachs and Anne Eichmann and Bernabeu, {Miguel O.} and Franco, {Claudio A.}",
note = "Funding Information: We thank the VML lab and Foundation Leducq ATTRACT members for helpful discussions. We thank Isabel Flores for helping with statistical analysis. Supercomputing time on the ARCHER UK National Supercomputing Service was provided by the “UK Consortium on Mesoscale Engineering Sciences (UKCOMES).” Funding: European Research Council: C.A.F. (679368); X.T. (883739). European Commission: C.A.F. and M.O.B. (801423); X.T. and P.R.-C. (731957). H2020-MSCA-PF grants to M.G.-G. (797621) and M.O. (842498). Fondation LeDucq: C.A.F. A.E. and M.O.B. (17CVD03). EPSRC: M.O.B. (EP/T008806/1; EP/R029598/1). Funda{\c c}{\~a}o para a Ci{\^e}ncia e Tecnologia: C.A.F. (PTDC/MED-PAT/31639/2017; PTDC/BIA-CEL/32180/2017; CEECIND/04251/2017). Spanish Ministry of Science and Innovation: P.R.-C. (PID2019-110298GB-I00); X.T. (PGC2018-099645-B-I00). Generalitat de Catalunya: X.T. and P.R.-C. (2017-SGR-1602). La Caixa Foundation: X.T. and P.R.-C. (LCF/PR/HR20/52400004). Fundaci{\'o} la Marat{\'o} de TV3: X.T. (201903-30-31-32). EMBO: L.M.F. (ALTF 2-2018), Conceptualization, P.B. M.D.-C. X.T. P.R.-C. M.O.B. and C.A.F.; methodology, P.B. M.D.-C. C.G.F. G.Z. L.M.F. M.O. M.G.-G. P.R.-C. M.O.B. and C.A.F.; experimentation and data acquisition, P.B. M.D.-C. C.G.F. G.Z. A. Pena, A. Pezzarossa, D.R. Y.G. M.O. D.B. I.C.F. L.H.M. I.M. Y.C. and C.A.F.; data analysis, P.B. M.D.-C. C.G.F. L.M.F. M.G.-G. Y.G. L.H.M. X.T. P.R.-C. A.E. M.O.B. and C.A.F.; project administration, C.A.F.; writing—original draft, C.A.F.; writing—review and editing, P.B. C.G.F. L.M.F. M.O. M.G.-G. A. Pena, A. Pezzarossa, I.C.F. X.T. P.R.-C. A.E. M.O.B. and C.A.F. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2022 The Author(s)",
year = "2022",
month = oct,
day = "10",
doi = "10.1016/j.devcel.2022.09.002",
language = "English",
volume = "57",
pages = "2321--2333.e9",
journal = "Developmental Cell",
issn = "1534-5807",
publisher = "Cell Press",
number = "19",
}