Semaphorin regulation of neural circuit assembly in the central nervous system

The assembly of neural circuits requires a wide array of molecular cues. These cues include secreted and transmembrane ligands and also the signaling receptors that together modulate axonal and dendritic morphology to promote functional neural connectivity during development. The semaphorin family of proteins and their various receptors serve this function. Many experiments demonstrate in vivo, and in multiple neural systems, how semaphorin-mediated regulation of neuronal morphology is critical for the regulation of neuronal connectivity. This system is nicely illustrated by recent work on semaphorin function in establishing neural connections in the olfactory and visual systems in both flies and mice. Further, semaphorins and their receptors regulate the elaboration of axon trajectories and precise targeting of these projections in the mammalian central nervous system, in addition to mediating axon pruning and also excitatory and inhibitory synaptogenesis. Taken together, these investigations into how semaphorins regulate neural connectivity provide insight into developmental mechanisms critical for neurite targeting, laminar-specific innervation, selective synapse formation, and neural circuit refinement.