Epicardial cell shape and maturation are regulated by Wt1 via transcriptional control of Bmp4

The epicardium plays a crucial role in embryonic heart development and adult heart repair; however, the molecular events underlying its maturation remain unknown. Wt1, one of the main markers of the embryonic epicardium, is essential for epicardial development and function. Here, we analyse the tran...

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Authors: Velecela, Victor; Torres Cano, Alejo; García Melero, Ana; Ramiro-Pareta, Marina; Müller Sánchez, Claudia Alejandra; Segarra Mondéjar, Marc; Chau, You-Ying; Campos Bonilla, Begoña; Reina del Pozo, Manuel; Soriano Zaragoza, Francesc X. (Francesc Xavier); Hastie, Nicholas D.; Martinez, Fernando O.; Martínez Estrada, Ofelia María
Format: Article
Status:Published version
Publication date:2019
Country:España
Institution:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repository:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/175561
Online Access:https://hdl.handle.net/2445/175561
Access Level:Open access
Keyword:Cèl·lules epitelials
Epithelial cells
Summary:The epicardium plays a crucial role in embryonic heart development and adult heart repair; however, the molecular events underlying its maturation remain unknown. Wt1, one of the main markers of the embryonic epicardium, is essential for epicardial development and function. Here, we analyse the transcriptomic profile of epicardial-enriched cells at different stages of development and from control and epicardial-specific Wt1 knockout (Wt1KO) mice. Transcriptomic and cell morphology analyses of epicardial cells from epicardial-specific Wt1KO mice revealed a defect in the maturation process of the mutant epicardium, including sustained upregulation of Bmp4 expression and the inability of mutant epicardial cells to transition into a mature squamous phenotype. We identified Bmp4 as a transcriptional target of Wt1, thus providing a molecular basis for the retention of the cuboidal cell shape observed in the Wt1KO epicardium. Accordingly, inhibition of the Bmp4 signalling pathway both ex vivo and in vivo rescued the cuboidal phenotype of the mutant epicardium. Our findings indicate the importance of the cuboidal-to-squamous transition in epicardial maturation, a process regulated by Wt1.

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