Abstract 20659: Interactions Between the Second Heart Field and Neural Crest Mediate Remodeling and Functional Maturation of the Semilunar Valves.
Cardiac defects represent the most prevalent congenital abnormality with many of these defects involving the cardiac valves. For example, bicuspid aortic valve disease affects 1-2% of the population and can lead to significant morbidity and mortality. The semilunar valves develop from embryonic endocardial cushions that contain extracellular matrix, mesenchyme derived from endothelial-mesenchymal transformation of endocardial cells, and neural crest cells. Here, we show a novel role for neural crest cells in semilunar valve remodeling. Using a series of genetically modified mouse models with second heart and/or neural crest defects, we show that abnormalities of cardiac neural crest result in dysmorphic, thickened semilunar valve leaflets that are functionally incompetent. These defects are caused by a lack of apoptosis that normally accompanies late gestation valve remodeling as well as an increase in extracellular matrix deposition. During migration to the outflow tract, we show neural crest cells interact with second heart field mesoderm, and that abnormal Notch signaling in second heart precursors results in defective neural crest migration and subsequent semilunar valve maturation. Our results suggest that neural crest cells provide an instructive signal for remodeling of the semilunar valves and highlight the importance of tissue-tissue interactions between the second heart field and neural crest during cardiogenesis.
- © 2010 by American Heart Association, Inc.