EXPRESSION OF FIBRONECTIN, THE INTEGRIN ALPHA-5, AND ALPHA-SMOOTH MUSCLE ACTIN IN HEART AND LUNG DEVELOPMENT

The developmentally regulated expression of fibronectin (FN) in developing organs and FN's ability to stimulate cell migration and differentiation in vitro suggest a role in organogenesis. We examined the distribution of FN and the alpha-5 subunit of its receptor, the integrin-alpha-5-beta-1, in the lungs and hearts of murine embryos at 11, 13, 16, and 18 days of gestation. In the lung, FN staining was present in the mesenchyme and parabronchial cells at day 11, increased at day 13, and decreased after day 16. Increases in FN coincided with the period of branching morphogenesis, and FN was concentrated at areas of airway bifurcation, suggesting a role for FN in cleft formation. The alpha-5 subunit appeared later at 13 days, co-distributing with FN only in well-developed primary bronchioles. At all stages, alpha-smooth muscle actin expression correlated temporally and spatially with that of the alpha-5 subunit. In the heart, staining for FN, the alpha-5 subunit, and alpha-smooth muscle actin were present at day 11 and increased at day 13. FN was present in the outflow tract and developing atria and ventricles, where it was concentrated in the outer layer or visceral pericardium. Interestingly, alpha-5 was detected at the inner layer, the endothelium, lining the outflow tract and atrioventricular cushions where endothelial cells migrate into the cardiac jelly in the process of epithelial-mesenchymal transformation. This suggests a potential role for alpha-5-beta-1 and FN in ventricular septation and valve formation. In contrast to the lung, alpha-5 expression in the heart preceded that of alpha-smooth muscle actin, particularly in the cushions and the trabecular zone of the ventricles. These observations suggest that the interaction of embryonic cells with FN may precede cell cytodifferentiation. FN and FN-binding integrins, including alpha-5-beta-1, may provide positional information necessary for lung branching and ventricular septation during development.