[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.
Fujisawa
Hajime
H
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.
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