Apoptosis in cardiac development

Cell degeneration, as a phenomenon accompanying developmental processes, wa s originally described over a century ago. Apoptosis, a term introduced app roximately three decades ago, has occupied investigators particularly with respect to cell and tissue kinetics, emphasizing its role in the disposal o f supernumerary, mal-instructed or damaged cells. Although apoptosis is mos tly related to developmental processes, evidence has been gathered indicati ng that it may also perform other roles. In this review, which concentrates on cardiac development, we examine focal apoptosis and subsequent signal c ascades in combination with timed morphogenetic events. Apoptosis mainly oc curs in the non-myocardial compartment of the embryonic heart, a compartmen t that consists of cells derived from the endocardium, the epicardium and t he neural crest. The last-mentioned population invades the outflow tract an d the atrioventricular endocardial cushions. The signalling cascade seems t o involve the activation of latent transforming growth factor beta, resulti ng in cardiomyocyte migration and subsequent myocardialization of the endoc ardial cushions. Aberrant apoptosis accompanies cardiac anomalies. Furtherm ore, an apoptotic population is found surrounding the developing conduction system. A possible role for differentiation is suggested.