VERSICAN EXPRESSION IS ASSOCIATED WITH CHAMBER SPECIFICATION, SEPTATION, AND VALVULOGENESIS IN THE DEVELOPING MOUSE HEART

The versican (PG-M) gene encodes a chondroitin sulfate proteoglycan th at is nonpermissive for cell migration and appears in association with slow cell proliferation and cytodifferentiation. Using the techniques of in situ hybridization and immunocytochemistry on sectioned mouse e mbryos, we found that the mRNA and protein for versican show similar d istributions and are expressed in a dynamic pattern during development of the heart. Versican exhibits generalized expression in the tubular heart but becomes rapidly downregulated in the atrium and exhibits hi gher transcript levels on the right side of the ventricular chamber th an the left, before the onset of ventricular septation. Versican is ex pressed strongly in the trabeculated ventricular myocardium, whereas t he compact proliferative zone has lower transcript abundance. It is ex pressed in the outer layers and on the crest of the ventricular septum and is prominent on the mesenchymal cap of the primary atrial septum. Versican is particularly strongly expressed in the endocardial cushio ns of the atrioventricular and outflow tract regions and in the atriov entricular, semilunar, and venous valves, This study raises the possib ility that versican may be involved in specification of the ventricula r chambers, in growth and fusion of the atrial and ventricular septa, and in the transformation from epithelium to mesenchyme that character izes development of the endocardial cushions. Versican may be a key pa rticipant in cardiogenesis, responding to the many diffusible signals that mediate interactions between the developing endocardium and myoca rdium.