The epicardium – the single-cell layer of mesothelium that surrounds the heart – harbours a population of progenitor cells that modulates heart development and contributes to various cardiac lineages. During heart development, these epicardium-derived progenitor cells (EPDCs) undergo epithelial-to-mesenchymal transition and migrate into the sub-epicardial space, but the mechanisms regulating their mobilization remain unclear. On p. 21, Eric Small and colleagues show that myocardin-related transcription factors (MRTFs) regulate the motility of mouse EPDCs as well as the maturation of coronary vessels. They demonstrate that MRTF-A and MRTF-B are enriched within the epicardium, where they localize to the perinuclear space. The researchers further demonstrate that, in epicardial-mesothelial cells cultured in vitro, TGFβ signalling leads to the nuclear accumulation of MRTFs and the activation of a cell motility gene expression program. Importantly, the epicardial-specific ablation of Mrtfa and Mrtfb causes sub-epicardial haemorrhage; mutant hearts display a disorganised epicardial layer. In addition, lineage-tracing studies reveal a novel epicardial-derived coronary pericyte population that contributes to coronary vessel integrity and that is depleted in mutant embryos. Together, these findings, which link EPDC motility to cell differentiation in the heart, highlight novel approaches that could be used to manipulate EPDCs for cardiac repair.