Semaphorins and the dynamic regulation of synapse assembly, refinement, and function.

•Semaphorins affect the spatial distribution of synapses by regulating dendritic arborization.•Semaphorins directly affect the formation of excitatory and inhibitory synapses.•Sema3E–PlexinD1 signaling is involved in pathway-specific CNS connectivity.•Semaphorins mediate synapse refinement during the pruning of exuberant neuronal connections.•Electrical activity can modulate neuronal responses to semaphorins during synapse refinement.