Cell signaling of adjacent cells. In cardiac muscle, gap junctions between adjacent cells allows for action potential propagation from the cardiac pacemaker region of the heart to spread and coordinately cause contraction of the heart. The notch signaling mechanism is an example of juxtacrine signaling (also known as contact-dependent signaling) in which two adjacent cells must make physical contact in order to communicate. This requirement for direct contact allows for very precise control of cell differentiation during embryonic development. In the worm "Caenorhabditis elegans", two cells of the developing gonad each have an equal chance of terminally differentiating or becoming a uterine
Cardiac neural crest cells the precursor to the pulmonary artery. In humans, mutations in Notch most often result in bicuspid aortic valve disease and calcification of the aortic valve. Bone morphogenetic proteins (BMPs) are required for neural crest cell migration into the cardiac cushions (precursors to heart valves and septa) and for differentiation of neural crest cells to smooth muscle cells of the aortic arch arteries. In neural crest–specific Alk2-deficient embryos, the cardiac cushions of the outflow tract are deficient in cells because of defects in neural crest cell migration. Fibroblast growth factor 8 (FGF8) transcription factors are essential for regulating the addition of