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...

Descripción completa

Detalles Bibliográficos
Autores: 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
Tipo de documento: Artículo
Estado:Published version
Fecha de publicación:2019
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/175561
Acceso en línea:https://hdl.handle.net/2445/175561
Nivel de acceso:Acceso abierto
Palabra clave:Cèl·lules epitelials
Epithelial cells
_version_ 1878732961771159552
author Velecela, Victor
author2 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
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author_browse Campos Bonilla, Begoña
Chau, You-Ying
García Melero, Ana
Hastie, Nicholas D.
Martinez, Fernando O.
Martínez Estrada, Ofelia María
Müller Sánchez, Claudia Alejandra
Ramiro-Pareta, Marina
Reina del Pozo, Manuel
Segarra Mondéjar, Marc
Soriano Zaragoza, Francesc X. (Francesc Xavier)
Torres Cano, Alejo
Velecela, Victor
author_facet 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
author_role author
collection Recercat. Dipósit de la Recerca de Catalunya
description 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.
eu_rights_str_mv openAccess
format article
id ES_4d5541a2ce4a2d6bf8e9fb2f965ef4bb
institution Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
network_acronym_str ES
network_name_str España
oai_identifier_str oai:recercat.cat:2445/175561
publishDate 2019
publishDateSort 2019
publisher The Company of Biologists
publisherStr The Company of Biologists
reponame_str Recercat. Dipósit de la Recerca de Catalunya
spelling Epicardial cell shape and maturation are regulated by Wt1 via transcriptional control of Bmp4 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 Cèl·lules epitelials Epithelial cells 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. The Company of Biologists https://hdl.handle.net/2445/175561
spellingShingle Epicardial cell shape and maturation are regulated by Wt1 via transcriptional control of Bmp4
Velecela, Victor
Cèl·lules epitelials
Epithelial cells
status_str publishedVersion
title Epicardial cell shape and maturation are regulated by Wt1 via transcriptional control of Bmp4
title_full Epicardial cell shape and maturation are regulated by Wt1 via transcriptional control of Bmp4
title_fullStr Epicardial cell shape and maturation are regulated by Wt1 via transcriptional control of Bmp4
title_full_unstemmed Epicardial cell shape and maturation are regulated by Wt1 via transcriptional control of Bmp4
title_short Epicardial cell shape and maturation are regulated by Wt1 via transcriptional control of Bmp4
title_sort Epicardial cell shape and maturation are regulated by Wt1 via transcriptional control of Bmp4
topic Cèl·lules epitelials
Epithelial cells
topic_facet Cèl·lules epitelials
Epithelial cells
url https://hdl.handle.net/2445/175561