Journal
PEDIATRIC CARDIOLOGY
Volume 30, Issue 5, Pages 643-650Publisher
SPRINGER
DOI: 10.1007/s00246-008-9368-z
Keywords
Notch; Cell communication; Cell fate specification; Cardiac valve development; EMT; Ventricular chamber development; Trabeculae; Valve degeneration; Ventricular noncompaction
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The Notch pathway is an ancient, highly conserved signaling mechanism that participates in essential cell-cell communication events between adjacent cells. Mutations in Notch-signaling elements cause cardiac abnormalities in mice and humans, demonstrating an essential role for Notch in heart development. Studies with targeted mutant mice indicate that Notch signaling promotes the epithelial-to-mesenchyme transition that gives rise to the cardiac valve primordium, which later is sculpted into mature valves. During ventricular chamber development, the myocardium differentiates into two layers: an outer compact zone and an inner trabecular zone. Trabeculae provide a pumping function during early phases of ventricular development and contribute to the cardiac conduction system in the mature heart. Notch regulates the endocardium-to-myocardium signals that balance proliferation and differentiation of trabecular myocytes. Recent evidence demonstrates that defective NOTCH signaling leads to aortic valve degeneration in humans. Future research will be informative about the involvement of altered NOTCH signaling in chamber abnormalities and other cardiac disorders.
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