Working model shows Notch-Wnt-Bmp signaling axis that regulates EMT and early valve formation.

<p><b>A</b>, Schematic showing the cardiac phenotypes found in the endocardial <i>Jagged1</i> or <i>Notch1</i> knockout embryos. During E9.5-E10.5, cushion endocardial cells undergo EMT and form endocardial cushions at the atrioventricular canal and outflow tract of the wild-type (WT) embryos. This process is disrupted in the endocardial <i>Jagged1</i> (<i>J1^f/f;c1^Cre</i>) or <i>Notch1</i> (<i>N1^f/f;c1^Cre</i>) knockout (KO) embryos, which results in hypocellular endocardial cushions. <b>B,</b> Endocardial Jagged1-mediated Notch1 activation induces expression of Wnt4, which subsequently upregulates expression of Bmp2 in the adjacent myocardium. Myocardial Bmp2 then acts on endocardial cells to promote EMT. This Notch-Wnt-Bmp signaling axis promotes EMT during heart valve development.