[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.
Group of Developmental Neurobiology and The 21 Century COE Program, Division of Biological Science, Nagoya University Graduate School of Science, Chikusa-ku, Nagoya, 464-8602 Japan.
Hajime
H
Fujisawa
D000818:Animals; D015815:Cell Adhesion Molecules / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D051379:Mice; D008817:Mice, Mutant Strains; D009415:Nerve Net / Q000254:growth & development*; D009419:Nerve Tissue Proteins / Q000502:physiology; D039961:Semaphorins / Q000502:physiology*
D015815:Cell Adhesion Molecules; D009419:Nerve Tissue Proteins; D039961:Semaphorins; C091529:plexin