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Notch signaling is essential for ventricular chamber development

Item Type:Article
Title:Notch signaling is essential for ventricular chamber development
Creators Name:Grego-Bessa, J. and Luna-Zurita, L. and del Monte, G. and Bolos, V. and Melgar, P. and Arandilla, A. and Garratt, A.N. and Zang, H. and Mukouyama, Y.S. and Chen, H. and Shou, W. and Ballestar, E. and Esteller, M. and Rojas, A. and Perez-Pomares, J.M. and de la Pompa, J.L.
Abstract:Ventricular chamber morphogenesis, first manifested by trabeculae formation, is crucial for cardiac function and embryonic viability and depends on cellular interactions between the endocardium and myocardium. We show that ventricular Notch1 activity is highest at presumptive trabecular endocardium. RBPJk and Notch1 mutants show impaired trabeculation and marker expression, attenuated EphrinB2, NRG1, and BMP10 expression and signaling, and decreased myocardial proliferation. Functional and molecular analyses show that Notch inhibition prevents EphrinB2 expression, and that EphrinB2 is a direct Notch target acting upstream of NRG1 in the ventricles. However, BMP10 levels are found to be independent of both EphrinB2 and NRG1 during trabeculation. Accordingly, exogenous BMP10 rescues the myocardial proliferative defect of in vitro-cultured RBPJk mutants, while exogenous NRG1 rescues differentiation in parallel. We suggest that during trabeculation Notch independently regulates cardiomyocyte proliferation and differentiation, two exquisitely balanced processes whose perturbation may result in congenital heart disease.
Source:Developmental Cell
Publisher:Cell Press
Page Range:415-429
Date:March 2007
Official Publication:https://doi.org/10.1016/j.devcel.2006.12.011
PubMed:View item in PubMed

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