Article

Coordinating Tissue Interactions: Notch Signaling in Cardiac Development and Disease

Program of Cardiovascular Developmental Biology, Department of Cardiovascular Development and Repair, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Melchor Fernández Almagro 3, E-28029 Madrid, Spain.
Developmental Cell (Impact Factor: 9.71). 02/2012; 22(2):244-54. DOI: 10.1016/j.devcel.2012.01.014
Source: PubMed

ABSTRACT

The Notch pathway is a crucial cell-fate regulator in the developing heart. Attention in the past centered on Notch function in cardiomyocytes. However, recent advances demonstrate that region-specific endocardial Notch activity orchestrates the patterning and morphogenesis of cardiac chambers and valves through regulatory interaction with multiple myocardial and neural crest signals. Notch also regulates cardiomyocyte proliferation and differentiation during ventricular chamber development and is required for coronary vessel specification. Here, we review these data and highlight disease connections, including evidence that Notch-Hey-Bmp2 interplay impacts adult heart valve disease and that Notch contributes to cardiac arrhythmia and pre-excitation syndromes.

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    • "The results of this study indicate a potential role of Notch signaling in the adult heart and suggest that it can be a therapeutic target for dilated cardiomyopathies. In humans, Notch signaling is important for the organogenesis of the heart (de la Pompa and Epstein, 2012) and mutations in NOTCH1 cause aortic valve disease (Garg et al., 2005). Although the importance of Notch signaling in mammalian heart development has been studied, its role in the adult heart, especially in a regenerative context, is an emerging area that has many unexplored questions (Ferrari and Rizzo, 2014). "
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    • "These genes are critical components of the NOTCH signaling pathway, which regulates various developmental processes. This pathway is involved in the morphogenesis of the heart and the partitioning of the heart by the left-right axis[14]. Ninety percent of individuals with this condition exhibit phenotypes characteristic of peripheral pulmonary hypoplasia, pulmonary stenosis, and TOF[15].: Macro-deletion syndromes, such as 3q, 4q, 5p, 8p, 9p, 11q, 13q, 18p, and 18q, are commonly associated with congenital heart defects. "
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    • "However , direct role of TEK has not been implicated with either Coats plus syndrome or dextrocardia phenotype till date. Notch signaling regulates cardiac development, septal development and coronary vascular development [18]. Cardiac septal abnormalities, like atrial septal defect, ventricular septal defect and coronary artery fistula have been reported in a few cases of Coats plus syndrome harboring compound heterozygous mutations in CTC1 [4]. "
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