Roles of semaphorins in neuron network formation]

A secreted semaphorin, Sema3A, is an axon guidance molecule that induces collapse of growth cones and repels axons in vitro. Neuropilin-1 (Nrp-1) is a receptor for Sema3A. To clarify the function of the semaphorin in vivo, we generated Sema3A mutant mice and Nrp-1 mutant mice by targeted disruption of the Sema3A and Nrp-1 genes, respectively. These mutant mouse embryos showed a severe defect in the trajectory and projection of PNS efferent, suggesting that the Nrp-1-mediated Sema3A signals play crucial roles in the directional guidance of nerve fibers and the establishment of PNS networks. The deprivation of Nrp-1-mediated Sema3A signals also induced disorganization of the sympathetic nervous system. In the Nrp-1 and Sema3A mutant mouse embryos, more than half of the TH-positive SG neurons were distributed at ectopic positions. As a whole, the sympathetic trunk was severely disorganized. Sema3 A recombinant proteins inhibited migration of the wild-type (Nrp-1-expressing) but not Nrp-1-deficient SG neurons in culture, suggesting that Nrp-1-mediated Sema3A inhibitory signals are essential in precise migration of SG neurons, as well as directional guidance of axons.