Temporally and spatially restricted expression of apolipoprotein J in the developing heart defines discrete stages of valve morphogenesis.

During cardiac valve morphogenesis, a series of interactions between the mesodermal-derived myocardium and the overlying endothelium lead to condensed leaflet structure formation. At the atrioventricular (AV) canal, endocardial cells are transformed by specialized underlying myocardial cells into endocardial cushions, and then remodeled into mitral and tricuspid valves. Aortic and pulmonary valves develop by a similar mechanism in the primitive outflow tract. Few genes exhibit restricted spatiotemporal expression in these critical embryonic structures, thus limiting the clues to the sequence of molecular events necessary for valvulogenesis. Apolipoprotein J (ApoJ), a secreted glycoprotein expressed in a variety of cell types at tissue interfaces, exhibits a highly restricted and dynamic expression pattern in the developing heart. ApoJ transcripts were detected in mice at day 9.0 of gestation in the wall of the developing truncus arteriosus. By day 10, intense signal occurred in a thin layer of myocardial cells adjacent to developing endocardial cushions of both atrioventricular canal and truncus arteriosus. No apoJ mRNA was present in the overlying endocardial cushions until 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 the developing heart implicates its role in the morphogenesis of the AV canal and outflow tract into cardiac valves.