Notch signaling promotes epithelial-mesenchymal transition (EMT) during cardiac development and oncogenic transformation. The study shows that Notch activity induces EMT through the transcriptional activation of Snail, a conserved EMT regulator. In the embryonic heart, Notch functions via lateral induction to promote TGFβ-mediated EMT, leading to the formation of cardiac valvular primordia. Embryos lacking Notch signaling exhibit reduced Snail expression, abnormal endocardial adhesion, and impaired EMT. Transient activation of Notch1 in zebrafish embryos results in hypercellular cardiac valves, while Notch inhibition prevents valve development. In vitro, overexpression of activated Notch1 in endothelial cells induces EMT and oncogenic transformation, accompanied by Snail upregulation and VE-cadherin repression. Notch is expressed in regions where EMT occurs, suggesting a fundamental role in both development and tumor progression. The study identifies Notch as a key regulator of EMT during cardiac development and oncogenesis, with Snail playing a central role in this process. Notch signaling is required for endocardial EMT, and its disruption leads to impaired EMT and valve development. The findings highlight the importance of Notch in regulating EMT and suggest that Notch may be reactivated during tumor metastasis.Notch signaling promotes epithelial-mesenchymal transition (EMT) during cardiac development and oncogenic transformation. The study shows that Notch activity induces EMT through the transcriptional activation of Snail, a conserved EMT regulator. In the embryonic heart, Notch functions via lateral induction to promote TGFβ-mediated EMT, leading to the formation of cardiac valvular primordia. Embryos lacking Notch signaling exhibit reduced Snail expression, abnormal endocardial adhesion, and impaired EMT. Transient activation of Notch1 in zebrafish embryos results in hypercellular cardiac valves, while Notch inhibition prevents valve development. In vitro, overexpression of activated Notch1 in endothelial cells induces EMT and oncogenic transformation, accompanied by Snail upregulation and VE-cadherin repression. Notch is expressed in regions where EMT occurs, suggesting a fundamental role in both development and tumor progression. The study identifies Notch as a key regulator of EMT during cardiac development and oncogenesis, with Snail playing a central role in this process. Notch signaling is required for endocardial EMT, and its disruption leads to impaired EMT and valve development. The findings highlight the importance of Notch in regulating EMT and suggest that Notch may be reactivated during tumor metastasis.