Abstract
The epicardium plays a crucial role in embryonic heart development and adult heart repair; however, the molecular events underlying its maturation remain unknown.
, 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
knockout (
) mice. Transcriptomic and cell morphology analyses of epicardial cells from epicardial-specific
mice revealed a defect in the maturation process of the mutant epicardium, including sustained upregulation of
expression and the inability of mutant epicardial cells to transition into a mature squamous phenotype. We identified
as a transcriptional target of Wt1, thus providing a molecular basis for the retention of the cuboidal cell shape observed in the
epicardium. Accordingly, inhibition of the Bmp4 signalling pathway both
and
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.