Semaphorin Signaling in Cardiovascular Development

Semaphorins were originally identified as neuronal guidance molecules mediating their attractive or repulsive signals by forming complexes with plexin and neuropilin receptors. Subsequent research has identified functions for semaphorin signaling in many organs and tissues outside of the nervous system. Vital roles for semaphorin signaling in vascular patterning and cardiac morphogenesis have been demonstrated, and impaired semaphorin signaling has been associated with various human cardiovascular disorders, including persistent truncus arteriosus, sinus bradycardia and anomalous pulmonary venous connections. Here, we review the functions of semaphorins and their receptors in cardiovascular development and disease and highlight important recent discoveries in the field. Semaphorin ligands and their receptors play diverse roles in many organs and tissues. In the cardiovascular system, a growing appreciation of the role of semaphorin signaling has emerged from studies of cardiac development and angiogenesis. Epstein et al. summarize recent advances and the relevance for understanding human cardiovascular diseases.