All tags Cardiovascular Epithelial-to-mesenchymal transition (EMT) in heart development

Epithelial-to-mesenchymal transition (EMT) in heart development

Epithelial-to-mesenchymal transition (EMT) is a biological process that allows a polarized epithelial cell to undergo multiple biochemical changes to become a mesenchymal cell that can migrate away from the epithelial layer in which it originated.

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EMT is a process of necessary for formation of 1) the mitral and tricuspid valves in the atrioventricular canal (AVC) and 2) the aortic and pulmonary valves in the outflow tract (OFT) region during development of the heart.

In the endocardium of AVC, Notch1 suppresses BMP2 activity through HEY1/2 activation while it promotes non-invasive EMT through activation of TGFβ​2 and SNAIL (SNAI1). BMP2, secreted from the adjacent myocardium, is necessary to trigger a complete invasion of endocardial cells by inducing SNAIL/SLUG (SNAI2) activity in conjunction with Notch1.

SNAIL directly interacts with MMP15 to induce mesenchymal phenotype in the endocardial cells. NFAT2 (NFATC1) acts in a cell-autonomous manner to suppress SNAIL/SLUG activity and inhibit EMT.

In the myocardium of OFT, Jagged1/Notch1 signaling stimulates FGF8 and BMP4 signaling. BMP4, in turn, signals to the endocardium to initiate EMT by stabilizing SNAIL/SLUG and by promoting neural crest cell differentiation, which will further contribute to OFT remodeling and septation.

References

  • MacGrogan D, Luna-Zurita L and de la Pompa JL (2011). Notch signaling in cardiac valve development and disease. Birth Defects Res A Clin Mol Teratol, 91(6), 449-59.

  • de la Pompa JL and Epstein JA (2012). Coordinating tissue interactions: Notch signaling in cardiac development and disease. Dev Cell, 22(2), 244-54.

  • Tao G, Levay AK, Gridley T and Lincoln J (2011). Mmp15 is a direct target of Snai1 during endothelial to mesenchymal transformation and endocardial cushion development. Dev Biol​, 359(2), 209-21.

  • Wu B, Wang Y, Lui W, Langworthy M, Tompkins KL, Hatzopoulos AK, Baldwin HS and Zhou B (2011). Nfatc1 coordinates valve endocardial cell lineage development required for heart valve formation. Circ Res, 109(2), 183-92.

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