FIBRONECTINS ARE ESSENTIAL FOR HEART AND BLOOD-VESSEL MORPHOGENESIS BUT ARE DISPENSABLE FOR INITIAL SPECIFICATION OF PRECURSOR CELLS

The underlying mechanisms of lethal cardiovascular defects associated with the fibronectin-null (FN.null) mutation in mouse embryos were inv estigated by lineage analysis of myocardial, endocardial, and endothel ial cells. A wide variation in phenotype was observed on two genetic b ackgrounds. In the less severe class (C57/BL6 background), FN.null emb ryos display a defective heart. Myocardial cells express the specific marker MF-20 and are correctly localized in the anterior trunk region, but myocardial organization is disrupted, resulting in a bulbous hear t tube. Endocardial cells express the specific marker platelet-endothe lial cell adhesion molecule-1 (PECAM-1) and are localized within the m yocardium, but the endocardium appears collapsed. Endothelial cells of two vascular beds are specified, but the aortae are distended and lac k contact with the surrounding mesenchyme, while no vessels form in th e yolk sac. Defects in the more severe class suggest that FNs are esse ntial earlier in development on the 129/Sv background. Myocardial and endocardial cells are specified, but morphogenesis of the myocardium a nd endocardium does not occur. Aortic endothelial cells are specified and localized normally, but remain scattered. Yolk sac endothelial cel ls resemble those of the less severe class. We conclude that FNs are e ssential for organization of heart and blood vessels, but are dispensa ble for cellular specification in the appropriate regions within the e mbryo. (C) 1997 by The American Society of Hematology.