Semaphorin3A

Semaphorin-3A (Sema3A) is a secreted member of the class-3 semaphorins that functions as a chemorepellent guidance cue in neural development. It influences axon pathfinding, neuronal migration, dendritic patterning, and synapse formation, and it also participates in vascular patterning and immune cell behavior.

Sema3A signals through a receptor complex that includes neuropilin-1 (NRP1) and one of the plexin-A family members (PLXNA1–PLXNA4). Binding of Sema3A to NRP1 forms a signaling unit with Plexin-As, triggering intracellular pathways that regulate the actin cytoskeleton via small GTPases such as RhoA, Rac1, and Cdc42. This leads to growth cone collapse or redirected axonal growth. The signaling can be modulated by heparan sulfate proteoglycans and by competition with vascular endothelial growth factor (VEGF) for NRP1 binding, linking neuronal guidance to angiogenic signaling.

Expression of Sema3A is prominent in the developing nervous system, including the forebrain, spinal cord, and retina, and persists in various tissues after development. It guides commissural axons at the midline, shapes cortical and hippocampal circuitry, and influences dendritic complexity and synapse maturation. In addition to neural roles, Sema3A affects endothelial cell behavior and vessel formation, contributing to anti-angiogenic effects in certain contexts.

Clinical relevance and research interest surround Sema3A’s involvement in neurodevelopmental and psychiatric conditions when signaling is perturbed, its potential anti-angiogenic properties in cancer biology, and its broader roles in immune regulation and sensory neuron innervation.