title: Anosmin-1 over-expression increases adult neurogenesis in the subventricular zone and neuroblast migration to the olfactory bulb.
abstract: New subventricular zone (SVZ)-derived neuroblasts that migrate via the rostral migratory stream are continuously added to the olfactory bulb (OB) of the adult rodent brain. Anosmin-1 (A1) is an extracellular matrix protein that binds to FGF receptor 1 (FGFR1) to exert its biological effects. When mutated as in Kallmann syndrome patients, A1 is associated with severe OB morphogenesis defects leading to anosmia and hypogonadotropic hypogonadism. Here, we show that A1 over-expression in adult mice strongly increases proliferation in the SVZ, mainly with symmetrical divisions, and produces substantial morphological changes in the normal SVZ architecture, where we also report the presence of FGFR1 in almost all SVZ cells. Interestingly, for the first time we show FGFR1 expression in the basal body of primary cilia in neural progenitor cells. Additionally, we have found that A1 over-expression also enhances neuroblast motility, mainly through FGFR1 activity. Together, these changes lead to a selective increase in several GABAergic interneuron populations in different OB layers. These specific alterations in the OB would be sufficient to disrupt the normal processing of sensory information and consequently alter olfactory memory. In summary, this work shows that FGFR1-mediated A1 activity plays a crucial role in the continuous remodelling of the adult OB.
authors.affiliation: Grupo de Neurobiología del Desarrollo-GNDe, Hospital Nacional de Parapléjicos, Toledo, Spain. d.garcia@dkfz-heidelberg.de.|Clinical Neurobiology, German Center for Cancer Research (DKFZ), Heidelberg, Germany. d.garcia@dkfz-heidelberg.de.
authors.forename: Diego
authors.initials: D
authors.lastname: García-González
authors.affiliation: Grupo de Neurobiología del Desarrollo-GNDe, Hospital Nacional de Parapléjicos, Toledo, Spain.|Instituto de Neurociencias, Universidad Miguel Hernández-CSIC, Alicante, Spain.
authors.forename: Verónica
authors.initials: V
authors.lastname: Murcia-Belmonte
authors.affiliation: Grupo de Neurobiología del Desarrollo-GNDe, Hospital Nacional de Parapléjicos, Toledo, Spain.
authors.forename: Pedro F
authors.initials: PF
authors.lastname: Esteban
authors.affiliation: University Medical Center Johannes Gutenberg, University of Mainz, Mainz, Germany.
authors.forename: Felipe
authors.initials: F
authors.lastname: Ortega
authors.affiliation: Instituto de Neurociencias de Castilla y León-INCyL, Universidad de Salamanca, Salamanca, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Díaz
authors.affiliation: Laboratorio de Neurobiología Comparada, Instituto Cavanilles, Universidad de Valencia, CIBERNED, Valencia, Spain.|Unidad mixta de Esclerosis múltiple y neurorregeneración, IIS Hospital La Fe, Valencia, Spain.
authors.forename: Irene
authors.initials: I
authors.lastname: Sánchez-Vera
authors.affiliation: Grupo de Neurobiología del Desarrollo-GNDe, Hospital Nacional de Parapléjicos, Toledo, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Lebrón-Galán
authors.affiliation: Departmento de Neurosciencias, Facultad de Medicina, Universidad del País Vasco, Leioa, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Escobar-Castañondo
authors.affiliation: Departmento de Neurosciencias, Facultad de Medicina, Universidad del País Vasco, Leioa, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Martínez-Millán
authors.affiliation: Instituto de Neurociencias de Castilla y León-INCyL, Universidad de Salamanca, Salamanca, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Weruaga
authors.affiliation: Laboratorio de Neurobiología Comparada, Instituto Cavanilles, Universidad de Valencia, CIBERNED, Valencia, Spain.
authors.forename: José Manuel
authors.initials: JM
authors.lastname: García-Verdugo
authors.affiliation: University Medical Center Johannes Gutenberg, University of Mainz, Mainz, Germany.
authors.forename: Benedikt
authors.initials: B
authors.lastname: Berninger
authors.affiliation: Grupo de Neurobiología del Desarrollo-GNDe, Hospital Nacional de Parapléjicos, Toledo, Spain. fdec@sescam.jccm.es.
authors.forename: Fernando
authors.initials: F
authors.lastname: de Castro
mesh_terms: D000818:Animals; D002455:Cell Division; D002465:Cell Movement; D002478:Cells, Cultured; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D006801:Humans; D007395:Interneurons / Q000378:metabolism / Q000502:physiology; D020547:Lateral Ventricles / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D008570:Memory, Short-Term / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D009434:Neural Pathways / Q000378:metabolism / Q000502:physiology / Q000648:ultrastructure; D055495:Neurogenesis; D009812:Odorants; D009830:Olfactory Bulb / Q000378:metabolism / Q000502:physiology*; D055696:Olfactory Perception / Q000502:physiology; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000378:metabolism*
chemical_list: C076266:ANOS1 protein, human; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; C496349:Fgfr1 protein, mouse; D051496:Receptor, Fibroblast Growth Factor, Type 1
keywords: Cell migration; FGF2; GnRH neuron; Interneuron; Kallmann syndrome; Neural stem cell; Primary cilium