Neuropilin receptors guide distinct phases of sensory and motor neuronal segmentation.

The segmented trunk peripheral nervous system is generated by ventrally migrating neural crest cells that exclusively invade the anterior sclerotome and differentiate into metameric dorsal root and sympathetic ganglia. Meanwhile, ventral spinal motor axons also project through the somites in a segmental fashion. How peripheral nervous system segmentation is generated is unknown. We previously showed that neuropilin 2 (Nrp2)/semaphorin 3F (Sema3F) signaling is required for segmental neural crest migration, but not for metameric dorsal root gangliogenesis. We now expand these results to show that Nrp2 patterns initial motor axon outgrowth as well. Later, Nrp1/Sema3A signaling is essential for segmental dorsal root gangliogenesis and motor axonal fasciculation into ventral roots. Strikingly, Nrp/Sema signaling is not required for sympathetic ganglia segmentation. These data show that Nrp2 and Nrp1 work together to produce segmentation of sensory and motor nerves, and that dorsal peripheral nervous system metamerism is generated in a stepwise, Nrp-dependent process.