title: Distinct roles of Nogo-a and Nogo receptor 1 in the homeostatic regulation of adult neural stem cell function and neuroblast migration.
abstract: In the adult mammalian subventricular zone (SVZ), GFAP-positive neural stem cells (NSCs) generate neuroblasts that migrate tangentially along the rostral migratory stream (RMS) toward the olfactory bulb (OB). In the mouse brain, we found that the plasticity inhibitors Nogo-A and Nogo receptor 1 (NgR1) are differentially expressed in the SVZ-OB system, in which Nogo-A identifies immature neuroblasts and NgR1 germinal astrocytes. We therefore examined the role of Nogo-A and NgR1 in the regulation of neurogenesis. Pharmacological experiments show that Nogo-66/NgR1 interaction reduces the proliferation of NSCs. This is consistent with a negative-feedback loop, in which newly generated neurons modulate cell division of SVZ stem cells. Moreover, the Nogo-A-Δ20 domain promotes neuroblast migration toward the OB through activation of the Rho/ROCK (Rho-associated, coiled-coil containing protein kinase) pathway, without the participation of NgR1. Our findings reveal a new unprecedented function for Nogo-A and NgR1 in the homeostatic regulation of the pace of neurogenesis in the adult mouse SVZ and in the migration of neuroblasts along the RMS.
authors.affiliation: Department of Neuroscience, University of Turin, I-10126 Turin, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Rolando
authors.forename: Roberta
authors.initials: R
authors.lastname: Parolisi
authors.forename: Enrica
authors.initials: E
authors.lastname: Boda
authors.forename: Martin E
authors.initials: ME
authors.lastname: Schwab
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Rossi
authors.forename: Annalisa
authors.initials: A
authors.lastname: Buffo
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D058851:GPI-Linked Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology; D006706:Homeostasis / Q000502:physiology*; D051379:Mice; D009185:Myelin Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D058953:Neural Stem Cells / Q000378:metabolism / Q000502:physiology*; D055495:Neurogenesis / Q000502:physiology*; D000070798:Nogo Proteins; D000070816:Nogo Receptor 1; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D054460:rho-Associated Kinases / Q000378:metabolism
chemical_list: D058851:GPI-Linked Proteins; D009185:Myelin Proteins; D000070798:Nogo Proteins; D000070816:Nogo Receptor 1; D011956:Receptors, Cell Surface; C000603201:Rtn4 protein, mouse; C419790:Rtn4r protein, mouse; D054460:rho-Associated Kinases