Article: Notch signaling is essential for ventricular chamber development.
2007 Volume 12, Issue 3, Page(s) 415–429
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 ... ...
| 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. |
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| MeSH term(s) | Animals ; Bone Morphogenetic Proteins/genetics ; Bone Morphogenetic Proteins/metabolism ; Cell Differentiation/physiology ; Cell Proliferation ; Ephrin-B2/genetics ; Ephrin-B2/metabolism ; Gene Expression Regulation, Developmental/physiology ; Heart/embryology ; Heart Ventricles/cytology ; Heart Ventricles/embryology ; Heart Ventricles/metabolism ; Mice ; Mutation/genetics ; Myoblasts, Cardiac/cytology ; Myoblasts, Cardiac/metabolism ; Myocytes, Cardiac/cytology ; Myocytes, Cardiac/metabolism ; Nerve Tissue Proteins/genetics ; Nerve Tissue Proteins/metabolism ; Neuregulin-1 ; Receptor, Notch1/genetics ; Receptor, Notch1/metabolism ; Receptors, Notch/genetics ; Receptors, Notch/metabolism ; Signal Transduction/physiology | ||||||||||
| Chemical Substances | Bmp10 protein, mouse ; Bone Morphogenetic Proteins ; Ephrin-B2 ; Nerve Tissue Proteins ; Neuregulin-1 ; Notch1 protein, mouse ; Nrg1 protein, mouse ; Receptor, Notch1 ; Receptors, Notch | ||||||||||
| Language | English | ||||||||||
| Publishing date | 2007-03 | ||||||||||
| Publishing country | United States | ||||||||||
| Document type | Journal Article ; Research Support, Non-U.S. Gov't | ||||||||||
| ZDB-ID | 2054967-2 | ||||||||||
| ISSN | 1878-1551 ; 1534-5807 | ||||||||||
| ISSN (online) | 1878-1551 | ||||||||||
| ISSN | 1534-5807 | ||||||||||
| DOI | 10.1016/j.devcel.2006.12.011 | ||||||||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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