title: IGF-I promotes neuronal migration and positioning in the olfactory bulb and the exit of neuroblasts from the subventricular zone.
abstract: While insulin-like growth factor-I (IGF-I) supports neuronal and glial differentiation in the CNS, it is largely unknown whether IGF-I also influences neuronal migration and positioning. We show here that the pattern of olfactory bulb (OB) layering is altered in Igf-I (-/-) mice. In these animals, Tbr1(+)-glutamatergic neurons are misplaced in the mitral cell layer (ML) and the external plexiform layer (EPL). In addition, there are fewer interneurons in the glomerular layer and the EPL of the Igf-I (-/-) mice, and fewer newborn neurons are incorporated into the OB from the forebrain subventricular zone (SVZ). Indeed, neuroblasts accumulate in the postnatal/adult SVZ of Igf-I (-/-) mice. Significantly, the positioning of Tbr1(+)-cells in a primitive ML is stimulated by IGF-I in cultured embryonic OB slices, an effect that is partially repressed by the phosphoinositide 3-kinase (PI3K) inhibitor. In OB cell cultures, IGF-I increases the phosphorylation of disabled1 (P-Dab1), an adaptor protein that is a target of Src family kinases (SFK) in the reelin signalling pathway, whereas reduced P-Dab1 levels were found in Igf-I (-/-) mice. Neuroblast migration from the rostral migratory stream (RMS) explants of postnatal Igf-I (-/-) was similar to that from Igf-I (+/+) explants. However, cell migration was significantly enhanced by IGF-I added to the explants, an effect that was repressed by PI3K and SFK inhibitors. These findings suggest that IGF-I promotes neuronal positioning in the OB and support a role for IGF-I in stimulating neuroblast exit from the SVZ into the RMS, thereby promoting the incorporation of newly formed neurons into the OB.
authors.affiliation: Instituto Cajal, Consejo Superior de Investigaciones Científicas, Madrid, Spain.
authors.forename: Anahí
authors.initials: A
authors.lastname: Hurtado-Chong
authors.forename: María J
authors.initials: MJ
authors.lastname: Yusta-Boyo
authors.forename: Eva
authors.initials: E
authors.lastname: Vergaño-Vera
authors.forename: Alessandro
authors.initials: A
authors.lastname: Bulfone
authors.forename: Flora
authors.initials: F
authors.lastname: de Pablo
authors.forename: Carlos
authors.initials: C
authors.lastname: Vicario-Abejón
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D015153:Blotting, Western; D002452:Cell Count; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D005455:Fluorescent Antibody Technique; D018698:Glutamic Acid / Q000378:metabolism; D017403:In Situ Hybridization; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D007395:Interneurons / Q000378:metabolism / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D046569:Neuroepithelial Cells / Q000378:metabolism; D055495:Neurogenesis; D009474:Neurons / Q000378:metabolism / Q000502:physiology; D009830:Olfactory Bulb / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D009924:Organ Culture Techniques; D010766:Phosphorylation / Q000502:physiology; D016548:Prosencephalon / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D000091042:Reelin Protein; D015398:Signal Transduction / Q000502:physiology; D013234:Stem Cells / Q000166:cytology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D000091042:Reelin Protein; D018698:Glutamic Acid; D007334:Insulin-Like Growth Factor I; D014446:Tyrosine 3-Monooxygenase; C000717128:Reln protein, mouse