Figure 2. Summary of cardiac developmental aspects of Notch signaling. A, Notch signaling affects AVC development via BMP 2/Tbx 2 pathway. B, Notch signaling initiates EMT via MMP-2, snail/VE-cadherin, VEGFR2/VEGF, and PI3K/Akt/eNOS pathways. EMT is a required step for valve development. C, Notch signaling promotes ventricular trabecular formation dependent on NRG1-ErbB2/4, Ephrin B2/Eph B4, and BMP-10 signaling pathways. D, Notch signaling stimulates smooth muscle differentiation during OFT development. E, Notch signaling modulates coronary vessel morphogenesis in which the embryonic epicardium actively participates. F, Notch signaling regulates cardiac conduction system function via effects on the atrioventricular node. AVC: atrioventricular canal; BMP-2: bone morphogenetic protein-2; Tbx2: T-box 2; EMT: epithelial-to-mesenchymal transition; MMP-2: matrix metalloproteinase-2; VEGFR 2: vascular endothelial growth factor receptor 2; VEGF: vascular endothelial growth factor; BMP-10: bone morphogenetic protein-10; OFT: outflow tract.