During cardiac morphogenesis, proepicardium cells envelop the myocardium to form the epicardium. Some epicardial cells subsequently undergo epithelial-to-mesenchymal transformation and invade the myocardium as epicardium-derived cells (EPDCs). This invasion step underlies the formation of the coronary vessels and fibrous matrix of the mature heart but how is it regulated? Michelle Combs, Katherine Yutzey and co-workers now reveal that NFATC1 promotes EPDC invasion into myocardium (see p. 1747). NFATC1, they report, is expressed in EPDCs in mouse and chick embryos and loss of its expression in EPDCs in mice decreases coronary vessel and fibrous matrix invasion into the myocardium. Other experiments in mouse embryos, chicken embryo hearts and isolated proepicardium cells indicate that NFATC1 activation by RANKL in EPDCs promotes expression of the extracellular matrix-degrading enzyme cathepsin K, promoting EPDC invasion into the myocardium. These new insights into heart morphogenesis, the authors suggest, could aid the development of EPDC-based therapies for cardiac diseases.

© 2011.
2011