Chapter Eleven - Notch Signaling in Cardiac Development and Disease

Abstract

The Notch-signaling pathway is involved in multiple processes during vertebrate cardiac development. Cardiomyocyte differentiation, patterning of the different cardiac regions, valve development, ventricular trabeculation, and outflow tract development have all been shown to depend on the activity of specific Notch-signaling elements. From these studies, it becomes obvious that Notch regulates in a cell autonomous or non-cell autonomous manner different signaling pathways, pointing to a role for Notch as a signal coordinator during cardiogenesis. While most of the research has concentrated on Notch signaling in the myocardium, the importance of Notch activity in the cardiac endothelium (endocardium) must not be overlooked. Endocardial Notch activity is crucial for valve and ventricular trabeculae development, two processes that illustrate the role of Notch as a signal coordinator. The importance of Notch signaling in human disease is evident from the discovery that many mutations in components of this pathway segregate in several inherited and acquired disorders. This reflects the fundamental roles that Notch performs during cardiac ontogeny. This review examines the experimental evidence supporting a role for Notch in cardiac development and adult heart homeostasis, and how dysregulated Notch signaling may lead to cardiac disease in the newborn and in the adult.