Misexpression of noggin leads to septal defects in the outflow tract of the chick heart

BMP-2 and BMP-4 are known to be involved in the early events which specify the cardiac lineage. Their later patterns of expression in the developing m ouse and chick heart, in the myocardium overlying the atrioventricular cana l (AV) and outflow tract (OFT) cushions, also suggest that they may play a role in valvoseptal development. In this study, we have used a recombinant retrovirus expressing noggin to inhibit the function of BMP-2/4 in the deve loping chick heart. This procedure resulted in abnormal development of the OFT and the ventricular septum. A spectrum of abnormalities was seen rangin g from common arterial trunk to double outlet right ventricle. In hearts in fected with noggin virus, where the neural crest cells have been labelled, the results show that BMP-2/4 function is required for the migration of neu ral crest cells into the developing OPT to form the aortopulmonary septum. Prior to septation, misexpression of noggin also leads to a decrease in the number of proliferating mesenchymal cells within the proximal cushions of the outflow tract. These results suggest that BMP-2/4 function may mediate several key events during cardiac development. (C) 2001 Academic Press.