ABSTRACT
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 mouse and chick heart, in the myocardium overlying the atrioventricular canal (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 developing chick heart. This procedure resulted in abnormal development of the OFT and the ventricular septum. A spectrum of abnormalities was seen ranging from common arterial trunk to double outlet right ventricle. In hearts infected 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 neural crest cells into the developing OFT 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.
Subject(s)
Heart Septal Defects/etiology , Heart/embryology , Proteins/genetics , Transforming Growth Factor beta , Animals , Bone Morphogenetic Protein 2 , Bone Morphogenetic Protein 4 , Bone Morphogenetic Proteins/genetics , Bone Morphogenetic Proteins/physiology , Carrier Proteins , Cell Division/physiology , Chick Embryo , In Situ Hybridization , Myocardium/metabolism , Neural Crest/cytology , PhenotypeABSTRACT
The vertebrate face develops from a series of primordia surrounding the primitive mouth and is thought to be patterned by the differential expression of homeobox-containing genes. Here we describe the isolation of the chick homologue of the homeobox-containing gene, Barx-1, and show its expression in the developing facial primordia, stomach, and appendicular skeleton. In the maxillary primordia, mesenchymal expression of Barx-1 is complementary to that of Msx-1, which correlate with overlying epithelial expression of Fgf-8 and Bmp-4, respectively. We show that epithelial signals are required to maintain Barx-1 expression and that FGF-8 can substitute for the epithelium. By contrast, BMPs reduce Barx-1 expression and can antagonize FGF-8 signaling. This suggests that in vivo, FGF-8/BMP signaling may regulate Barx-1 gene expression. This provides evidence that the differential expression of FGF-8 and BMPs may determine homeobox-containing gene expression and hence patterning of the facial primordia.
