Endothelial deletion of Wt1 disrupts coronary angiogenesis and myocardium development

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  • dc.contributor.author Ramiro Pareta, Marina
  • dc.contributor.author Müller-Sánchez, Claudia
  • dc.contributor.author Portella-Fortuny, Rosa
  • dc.contributor.author Soler-Botija, Carolina
  • dc.contributor.author Torres-Cano, Alejo
  • dc.contributor.author Esteve-Codina, Anna
  • dc.contributor.author Bayés-Genís, Antoni
  • dc.contributor.author Reina, Manuel
  • dc.contributor.author Soriano, Francesc X.
  • dc.contributor.author Montanez, Eloi
  • dc.contributor.author Martínez Estrada, Ofelia M.
  • dc.date.accessioned 2023-06-16T06:11:08Z
  • dc.date.available 2023-06-16T06:11:08Z
  • dc.date.issued 2023
  • dc.description.abstract Wt1 encodes a zinc finger protein that is crucial for epicardium development. Although WT1 is also expressed in coronary endothelial cells (ECs), the abnormal heart development observed in Wt1 knockout mice is mainly attributed to its functions in the epicardium. Here, we have generated an inducible endothelial-specific Wt1 knockout mouse model (Wt1KOΔEC). Deletion of Wt1 in ECs during coronary plexus formation impaired coronary blood vessels and myocardium development. RNA-Seq analysis of coronary ECs from Wt1KOΔEC mice demonstrated that deletion of Wt1 exerted a major impact on the molecular signature of coronary ECs and modified the expression of several genes that are dynamically modulated over the course of coronary EC development. Many of these differentially expressed genes are involved in cell proliferation, migration and differentiation of coronary ECs; consequently, the aforementioned processes were affected in Wt1KOΔEC mice. The requirement of WT1 in coronary ECs goes beyond the initial formation of the coronary plexus, as its later deletion results in defects in coronary artery formation. Through the characterization of these Wt1KOΔEC mouse models, we show that the deletion of Wt1 in ECs disrupts physiological blood vessel formation.
  • dc.description.sponsorship This work was supported by the Ministerio de Ciencia e Innovación/Agencia Estatal de Investigación (PID2020-119315GB-I00 to O.M.M.-E., PID 2019-108902 GB-I00 to E.M. and PID2020-119322GB-I00 to F.X.S.), by “la Caixa” Foundation (LCF/PR/HR17/52150009 to O.M.M.-E.), by the Sociedad Española de Cardiología (Basic Research Grant in Cardiology, 2018 to O.M.M.-E.) and by Centro de Investigación Biomédica en Red Enfermedades Cardiovasculares projects as a part of the Plan Nacional de I+D+I (CB16/11/00403 to A.B.-G.). A.E.-C. was funded by the Instituto de Salud Carlos III/Ministerio de Economía y Competitividad (PT17/0009/0019). Open Access funding provided by the Universitat de Barcelona. Deposited in PMC for immediate release.
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Ramiro-Pareta M, Müller-Sánchez C, Portella-Fortuny R, Soler-Botija C, Torres-Cano A, Esteve-Codina A, et al. Endothelial deletion of Wt1 disrupts coronary angiogenesis and myocardium development. Development. 2023 Mar;150(6):dev201147. DOI: 10.1242/dev.201147
  • dc.identifier.doi http://dx.doi.org/10.1242/dev.201147
  • dc.identifier.issn 0950-1991
  • dc.identifier.uri http://hdl.handle.net/10230/57182
  • dc.language.iso eng
  • dc.publisher Company of Biologists
  • dc.relation.ispartof Development. 2023 Mar;150(6):dev201147
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2020-119315GB-I00
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2019-108902GB-I00
  • dc.rights © 2023. Published by The Company of Biologists Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0
  • dc.subject.keyword Angiogenesis
  • dc.subject.keyword Blood vessel formation
  • dc.subject.keyword Coronary endothelial cells
  • dc.subject.keyword Heart development
  • dc.subject.keyword WT1
  • dc.title Endothelial deletion of Wt1 disrupts coronary angiogenesis and myocardium development
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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