TEMPORALLY AND SPATIALLY RESTRICTED EXPRESSION OF APOLIPOPROTEIN-J INTHE DEVELOPING HEART DEFINES DISCRETE STAGES OF VALVE MORPHOGENESIS

During cardiac valve morphogenesis, a series of interactions between t he mesodermal-derived myocardium and the overlying endothelium lead to condensed leaflet structure formation. At the atrioventricular (AV) c anal, endocardial cells are transformed by specialized underlying myoc ardial cells into endocardial cushions, and then remodeled into mitral and tricuspid valves. Aortic and pulmonary valves develop by a simila r mechanism in the primitive outflow tract. Few genes exhibit restrict ed spatiotemporal expression in these critical embryonic structures, t hus limiting the clues to the sequence of molecular events necessary f or valvulogenesis. Apolipoprotein J (ApoJ), a secreted glycoprotein ex pressed in a variety of cell types at tissue interfaces, exhibits a hi ghly restricted and dynamic expression pattern in the developing heart . ApoJ transcripts were detected in mice at day 9.0 of gestation in th e wall of the developing truncus arteriosus. By day 10, intense signal occurred in a thin layer of myocardial cells adjacent to developing e ndocardial cushions of both atrioventricular canal and truncus arterio sus. No apoJ mRNA was present in the overlying endocardial cushions un til day 13.5 when prevalvular condensation begins. Intense expression occurred in the stromal connective tissue throughout leaflet formation . The highly restricted spatiotemporal expression pattern of apoJ in t he developing heart implicates its role in the morphogenesis of the AV canal and outflow tract into cardiac valves. (C) 1994 Wiley-Liss, Inc .