title: Axonal branching in lateral olfactory tract is promoted by Nogo signaling.
abstract: Mitral cells are major projection neurons of the olfactory bulb (OB) that form an axonal bundle known as the lateral olfactory tract (LOT). After axonal bundle formation, collateral branches sprout from primary axons of the LOT. Recently, we identified LOT usher substance (LOTUS) as an endogenous Nogo receptor-1 (NgR1) antagonist and demonstrated that LOTUS contributes to the formation of the LOT axonal bundle. Immunoblots revealed that the expression level of Nogo-A in the OB developmentally increased during axonal collateral formation. Next, we found that the axonal collateral branches were increased in cultured OB neurons from LOTUS-knockout (KO) mice, whereas they were decreased in cultured OB neurons from NgR1-KO mice. Knockdown of Nogo-A in cultured OB neurons reduced the number of axonal collateral branches, suggesting that endogenous Nogo-A induces axonal branching. Finally, the collateral branches of the LOT were increased in LOTUS-KO mice, whereas those in NgR1-KO mice were decreased. Moreover, the abnormal increase of axonal branching observed in LOTUS-KO mice was rescued in the double mutant of LOTUS- and NgR1-KO mice. These findings suggest that Nogo-A and NgR1 interactions may contribute to axonal branching in LOT development.
authors.affiliation: Molecular Medical Bioscience Laboratory, Department of Medical Life Science, Yokohama City University Graduate School of Medical Life Science, Yokohama 230-0045, Japan.
authors.forename: Masumi
authors.initials: M
authors.lastname: Iketani
authors.affiliation: Molecular Medical Bioscience Laboratory, Department of Medical Life Science, Yokohama City University Graduate School of Medical Life Science, Yokohama 230-0045, Japan.|Department of Neurosurgery, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan.
authors.forename: Takaakira
authors.initials: T
authors.lastname: Yokoyama
authors.affiliation: Molecular Medical Bioscience Laboratory, Department of Medical Life Science, Yokohama City University Graduate School of Medical Life Science, Yokohama 230-0045, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kurihara
authors.affiliation: Department of Neurology and Section of Neurobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Strittmatter
authors.affiliation: Department of Molecular Pharmacology and Neurobiology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Goshima
authors.affiliation: Department of Neurosurgery, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan.
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Kawahara
authors.affiliation: Molecular Medical Bioscience Laboratory, Department of Medical Life Science, Yokohama City University Graduate School of Medical Life Science, Yokohama 230-0045, Japan.
authors.forename: Kohtaro
authors.initials: K
authors.lastname: Takei
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology*; D002135:Calcium-Binding Proteins / Q000502:physiology; D002478:Cells, Cultured; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation; D009474:Neurons / Q000502:physiology; D000070798:Nogo Proteins / Q000502:physiology*; D000070816:Nogo Receptor 1 / Q000502:physiology; D009830:Olfactory Bulb / Q000196:embryology* / Q000502:physiology*; D016548:Prosencephalon / Q000502:physiology; D015398:Signal Transduction
chemical_list: D002135:Calcium-Binding Proteins; C560339:Crtac1 protein, mouse; D000070798:Nogo Proteins; D000070816:Nogo Receptor 1; C000603201:Rtn4 protein, mouse; C419790:Rtn4r protein, mouse