The Role of Neuropilin-1/Semaphorin 3A Signaling in Lymphatic Vessel Development and Maturation

During development, the lymphatic and the blood vascular system form highly branched networks that show extensive architectural similarities with the peripheral nervous system. Increasing evidence suggests that the vascular and the nervous systems share signaling pathways to overcome common challenges such as guidance of growth and patterning. Semaphorins, a large group of proteins originally identified as axon guidance molecules with repelling function, and their receptors, neuropilins and plexins, have recently also been implicated in vascular development. Here, we summarize the role of semaphorins and their receptors in angiogenesis and lymphangiogenesis, with an emphasis on neuropilin-1/semaphorin 3A interactions in lymphatic vessel maturation and valve formation. Understanding the basic principles of lymphatic vessel development and maturation might facilitate the development of therapies for the treatment of human diseases associated with lymphedema.