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. Bernabeu; Cláudio A. Franco

doi:10.1016/j.devcel.2022.09.002

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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

12 Citations (Scopus)

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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.

Original language	English
Pages (from-to)	2321–2333
Number of pages	23
Journal	Developmental Cell
Volume	57
Issue number	19
DOIs	https://doi.org/10.1016/j.devcel.2022.09.002
Publication status	Published - 10 Oct 2022

Keywords

Angiogenesis
Cell polarity
Mechanobiology
Morphogenesis
Shear stress

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Barbacena, P., Dominguez-Cejudo, M., Fonseca, C. G., Gómez-González, M., Faure, L. M., Zarkada, G., Pena, A., Pezzarossa, A., Ramalho, D., Giarratano, Y., Ouarné, M., Barata, D., Fortunato, I. C., Misikova, L. H., Mauldin, I., Carvalho, Y., Trepat, X., Roca-Cusachs, P., Eichmann, A., ... Franco, C. A. (2022). Competition for endothelial cell polarity drives vascular morphogenesis in the mouse retina. Developmental Cell, 57(19), 2321–2333. https://doi.org/10.1016/j.devcel.2022.09.002

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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 = "Angiogenesis, Cell polarity, Mechanobiology, Morphogenesis, Shear stress",

author = "Pedro Barbacena and Maria Dominguez-Cejudo and Fonseca, {Catarina G.} and Manuel G{\'o}mez-Gonz{\'a}lez and Faure, {Laura M.} and Georgia Zarkada and Andreia Pena and Anna Pezzarossa and Daniela Ramalho and Ylenia Giarratano and Marie Ouarn{\'e} and David Barata and Fortunato, {Isabela C.} and Misikova, {Lenka Henao} and Ian Mauldin and Yulia Carvalho and Xavier Trepat and Pere Roca-Cusachs and Anne Eichmann and Bernabeu, {Miguel O.} and Franco, {Cl{\'a}udio 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",

journal = "Developmental Cell",

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Barbacena, P, Dominguez-Cejudo, M, Fonseca, CG, Gómez-González, M, Faure, LM, Zarkada, G, Pena, A, Pezzarossa, A, Ramalho, D, Giarratano, Y, Ouarné, M, Barata, D, Fortunato, IC, Misikova, LH, Mauldin, I, Carvalho, Y, Trepat, X, Roca-Cusachs, P, Eichmann, A, Bernabeu, MO & Franco, CA 2022, 'Competition for endothelial cell polarity drives vascular morphogenesis in the mouse retina', Developmental Cell, vol. 57, no. 19, pp. 2321–2333. https://doi.org/10.1016/j.devcel.2022.09.002

TY - JOUR

T1 - Competition for endothelial cell polarity drives vascular morphogenesis in the mouse retina

AU - Barbacena, Pedro

AU - Dominguez-Cejudo, Maria

AU - Fonseca, Catarina G.

AU - Gómez-González, Manuel

AU - Faure, Laura M.

AU - Zarkada, Georgia

AU - Pena, Andreia

AU - Pezzarossa, Anna

AU - Ramalho, Daniela

AU - Giarratano, Ylenia

AU - Ouarné, Marie

AU - Barata, David

AU - Fortunato, Isabela C.

AU - Misikova, Lenka Henao

AU - Mauldin, Ian

AU - Carvalho, Yulia

AU - Trepat, Xavier

AU - Roca-Cusachs, Pere

AU - Eichmann, Anne

AU - Bernabeu, Miguel O.

AU - Franco, Cláudio A.

N1 - 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). Fundação para a Ciência 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). Fundació la Marató 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: © 2022 The Author(s)

PY - 2022/10/10

Y1 - 2022/10/10

N2 - 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.

AB - 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.

KW - Angiogenesis

KW - Cell polarity

KW - Mechanobiology

KW - Morphogenesis

KW - Shear stress

UR - http://www.scopus.com/inward/record.url?scp=85139362088&partnerID=8YFLogxK

U2 - 10.1016/j.devcel.2022.09.002

DO - 10.1016/j.devcel.2022.09.002

M3 - Article

C2 - 36220082

AN - SCOPUS:85139362088

SN - 1534-5807

VL - 57

SP - 2321

EP - 2333

JO - Developmental Cell

JF - Developmental Cell

IS - 19

ER -

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

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Keywords

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