| Atrioventricular septation (AV) is dependent upon the proper formation and interaction of the AV cushions, the mesenchymal cap of the primary atrial septum, and the Dorsal Mesenchymal Protrusion (DMP). Of these AV mesenchymal components, only the DMP forms from Second Heart Field progenitors. More recently, studies have shown that impaired DMP development results in Atrioventricular Septal Defect (AVSD). The molecular pathways underpinning DMP development, however, have yet to be fully elucidated.;Bone Morphogenetic Proteins (BMPs) are required for numerous developmental cardiac events. In preliminary studies, we observed expression of markers associated with active BMP signaling in the region from which the DMP develops. Conditional deletion of the BMP receptor Alk3 from the SHF resulted in impaired formation of the DMP and a fully penetrant AVSD phenotype. Analysis of the venous pole revealed a reduction in proliferative index and number of SHF cells. The AV cushions, in contrast, were not significantly altered with respect to volume, proliferation, or expression of markers associated with active BMP/TGFbeta signaling. |
