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

Autor:	Velecela V; Celltec-UB, Department of Cell Biology, Physiology and Immunology, Faculty of Biology, University of Barcelona, Barcelona 08028, Spain.; MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Edinburgh EH4 2XU, UK., Torres-Cano A; Celltec-UB, Department of Cell Biology, Physiology and Immunology, Faculty of Biology, University of Barcelona, Barcelona 08028, Spain.; Institute of Biomedicine (IBUB), University of Barcelona, Barcelona 08028, Spain., García-Melero A; Celltec-UB, Department of Cell Biology, Physiology and Immunology, Faculty of Biology, University of Barcelona, Barcelona 08028, Spain.; Institute of Biomedicine (IBUB), University of Barcelona, Barcelona 08028, Spain., Ramiro-Pareta M; Celltec-UB, Department of Cell Biology, Physiology and Immunology, Faculty of Biology, University of Barcelona, Barcelona 08028, Spain.; Institute of Biomedicine (IBUB), University of Barcelona, Barcelona 08028, Spain., Müller-Sánchez C; Celltec-UB, Department of Cell Biology, Physiology and Immunology, Faculty of Biology, University of Barcelona, Barcelona 08028, Spain., Segarra-Mondejar M; Celltec-UB, Department of Cell Biology, Physiology and Immunology, Faculty of Biology, University of Barcelona, Barcelona 08028, Spain.; Institut de Neurociències, Universitat de Barcelona, Barcelona 08028, Spain., Chau YY; Centre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, UK., Campos-Bonilla B; Department of Basic Clinical Practice, University of Barcelona, Barcelona 08036, Spain., Reina M; Celltec-UB, Department of Cell Biology, Physiology and Immunology, Faculty of Biology, University of Barcelona, Barcelona 08028, Spain., Soriano FX; Celltec-UB, Department of Cell Biology, Physiology and Immunology, Faculty of Biology, University of Barcelona, Barcelona 08028, Spain.; Institut de Neurociències, Universitat de Barcelona, Barcelona 08028, Spain., Hastie ND; MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Edinburgh EH4 2XU, UK., Martínez FO; School of Biosciences and Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XH, UK., Martínez-Estrada OM; Celltec-UB, Department of Cell Biology, Physiology and Immunology, Faculty of Biology, University of Barcelona, Barcelona 08028, Spain ofeliamartinez@ub.edu.; Institute of Biomedicine (IBUB), University of Barcelona, Barcelona 08028, Spain.
Jazyk:	angličtina
Zdroj:	Development (Cambridge, England) [Development] 2019 Oct 17; Vol. 146 (20). Date of Electronic Publication: 2019 Oct 17.
DOI:	10.1242/dev.178723
Abstrakt:	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. Competing Interests: Competing interestsThe authors declare no competing or financial interests. (© 2019. Published by The Company of Biologists Ltd.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu