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Title

IGF-I promotes neuronal migration and positioning in the olfactory bulb and the exit from the subventricular zone

AuthorsHurtado-Chong, Anahí ; Yusta-Boyo, María J.; Vergaño-Vera, Eva ; Bulfone, Alessandro; Pablo, Flora de ; Vicario-Abejón, Carlos
KeywordsIGF-I
Neuronal migration and positioning
Olfactory bulb
Phosphoinositide 3-kinase (PI3K)
Src family kinases (SFK)
Subventricular zone
Issue DateSep-2009
PublisherBlackwell Publishing
CitationEuropean Journal of Neuroscience 30(5):742-755 (2009)
AbstractWhile 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
Description52 p.-8 fig.-4 supl.fig.
Publisher version (URL)http://dx.doi.org/10.1111/j.1460-9568.2009.06870.x
URIhttp://hdl.handle.net/10261/53655
DOI10.1111/j.1460-9568.2009.06870.x
ISSN0953-816X
E-ISSN1460-9568
Appears in Collections:(CIB) Artículos
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