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Non-canonical Wnt signaling regulates junctional mechanocoupling during angiogenic collective cell migration

2019Artigo científico Acesso aberto
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dc.contributor.authorCarvalho, Joana R.
dc.contributor.authorFortunato, Isabela C.
dc.contributor.authorFonseca, Catarina
dc.contributor.authorPezzarossa, Anna
dc.contributor.authorBarbacena, Pedro
dc.contributor.authorDominguez-Cejudo, Maria Angeles
dc.contributor.authorVasconcelos, Francisca
dc.contributor.authorSantos, Nuno C.
dc.contributor.authorCarvalho, Filomena Almeida
dc.contributor.authorFranco, Claudio
dc.date.accessioned2021-05-25T12:08:55Z
dc.date.available2021-05-25T12:08:55Z
dc.date.issued2019
dc.description© 2019, Carvalho et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.pt_PT
dc.description.abstractMorphogenesis 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.pt_PT
dc.description.sponsorshipResearch was supported by European Research Council starting grant (679368), the H2020-Twinning grant (692322), the Fundação para a Ciência e a Tecnologia funding (grants: IF/00412/2012; EXPL-BEX-BCM-2258–2013; PRECISE-LISBOA-01–0145-FEDER-016394; UID/BIM/50005/2019, a project funded by Fundação para a Ciência e a Tecnologia (FCT)/ Ministério da Ciência,Tecnologia e Ensino Superior (MCTES) through Fundos do Orçamento de Estado; and a grant from the Fondation Leducq (17CVD03); and personal fellowships: BD/52224/2013​​ to JRC, BD/105856/2014 to PB, and BD/128375/2017 to CF) and LISBOA-01–0145-FEDER-007391, project cofunded by FEDER, through POR Lisboa 2020 - Programa Operacional Regional de Lisboa, PORTUGAL 2020, and Fundação para a Ciência e a Tecnologia.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationElife. 2019 Jun 27;8:e45853pt_PT
dc.identifier.doi10.7554/eLife.45853pt_PT
dc.identifier.eissn2050-084X
dc.identifier.urihttp://hdl.handle.net/10451/48132
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publishereLife Sciences Publicationspt_PT
dc.relationIF/00412/2012pt_PT
dc.relationPRINCIPLES OF AXIAL POLARITY-DRIVEN VASCULAR PATTERNING
dc.relationTowards outstanding research and training in tumour biology at IMM
dc.relation17CVD03pt_PT
dc.relationInstituto de Medicina Molecular
dc.relationBD/128375/2017pt_PT
dc.relationFORCE TRANSMISSION AND ENDOTHELIAL CELL REARRANGEMENTS DURING VASCULAR REMODELING
dc.relation.publisherversionhttps://elifesciences.org/pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.titleNon-canonical Wnt signaling regulates junctional mechanocoupling during angiogenic collective cell migrationpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitlePRINCIPLES OF AXIAL POLARITY-DRIVEN VASCULAR PATTERNING
oaire.awardTitleTowards outstanding research and training in tumour biology at IMM
oaire.awardTitleInstituto de Medicina Molecular
oaire.awardTitleFORCE TRANSMISSION AND ENDOTHELIAL CELL REARRANGEMENTS DURING VASCULAR REMODELING
oaire.awardURIinfo:eu-repo/grantAgreement/EC/H2020/679368/EU
oaire.awardURIinfo:eu-repo/grantAgreement/EC/H2020/692322/EU
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UID%2FBIM%2F50005%2F2019/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//PD%2FBD%2F52224%2F2013/PT
oaire.citation.titleeLifept_PT
oaire.citation.volume8pt_PT
oaire.fundingStreamH2020
oaire.fundingStreamH2020
oaire.fundingStream6817 - DCRRNI ID
person.familyNameFonseca
person.familyNamePezzarossa
person.familyNameBarbacena
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project.funder.identifierhttp://doi.org/10.13039/501100008530
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project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameEuropean Commission
project.funder.nameEuropean Commission
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
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rcaap.typearticlept_PT
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