Fig. 8.

Model for JAG1-Notch signaling in the ductus arteriosus and descending aorta. In the ductus arteriosus and descending aorta of wild-type mice, endothelial cells expressing JAG1 protein undergo heterotypic interactions with adjacent vascular mural/smooth muscle cells expressing Notch receptors (most likely through NOTCH1, although a role for NOTCH3 cannot be excluded). Notch signal reception via lateral induction induces JAG1 expression in the receiving cells, leading to JAG1-mediated Notch signal transmission through homotypic interactions with the adjacent layer of smooth muscle cells. We further propose that Notch signal reception by vascular smooth muscle cells is required for their differentiation into contractile, rather than synthetic, smooth muscle cells. In embryos with endothelial cell-specific Jag1 deletion, the mutant endothelial cells are unable to signal to adjacent smooth muscle cells, which consequently differentiate into synthetic smooth muscle cells. In embryos with smooth muscle cell-specific Jag1 deletion, JAG1-expressing endothelial cells signal heterotypically to the adjacent layer of mutant vascular smooth muscle cells. These cells differentiate as contractile smooth muscle and upregulate expression of the mutant JAG1 protein. However, these mutant smooth muscle cells are unable to propagate the JAG1 signal through homotypic cellular interactions to more distal layers of smooth muscle, which therefore differentiate as synthetic smooth muscle cells.