Ramiro Pareta, MarinaMüller-Sánchez, ClaudiaPortella-Fortuny, RosaSoler-Botija, CarolinaTorres-Cano, AlejoEsteve-Codina, AnnaBayés-Genís, AntoniReina, ManuelSoriano, Francesc X.Montanez, EloiMartínez Estrada, Ofelia M.2023-06-162023-06-162023Ramiro-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.2011470950-1991http://hdl.handle.net/10230/57182Wt1 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.application/pdfeng© 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.info:eu-repo/semantics/articlehttp://dx.doi.org/10.1242/dev.201147AngiogenesisBlood vessel formationCoronary endothelial cellsHeart developmentWT1info:eu-repo/semantics/openAccess