2026-09-08T03:05:14Zhttps://gredos.usal.es/oai/request
oai:gredos.usal.es:10366/1696902026-02-11T01:00:55Zcom_10366_3948com_10366_3947com_10366_3946com_10366_3823col_10366_3949
Gestión del Repositorio Documental de la Universidad de Salamanca author Gómez Rodríguez, Carmela author Jimeno García, David author Fernández Medarde, Alberto author García Navas, Rósula Mercedes author Calzada, Nuria author Santos de Dios, Eugenio Miguel 2026-02-10T10:11:03Z 2026-02-10T10:11:03Z 2017 Gómez, C., Jimeno, D., Fernández-Medarde, A., García-Navas, R., Calzada, N., & Santos, E. (2017). Ras-GRF2 regulates nestin-positive stem cell density and onset of differentiation during adult neurogenesis in the mouse dentate gyrus. Molecular and Cellular Neuroscience, 85, 127-147. https://doi.org/10.1016/J.MCN.2017.09.006 1044-7431 http://hdl.handle.net/10366/169690 10.1016/j.mcn.2017.09.006 1095-9327 [EN]Various parameters of neurogenesis were analyzed in parallel in the two neurogenic areas (the Dentate Gyrus[DG] and the Subventricular Zone[SVZ]/Rostral Migratory Stream[RMS]/Main Olfactory Bulb[MOB] neurogenic system) of adult WT and KO mouse strains for the Ras-GRF1/2 genes (Ras-GRF1-KO, Ras-GRF2-KO, Ras-GRF1/2-DKO). Significantly reduced numbers of doublecortin[DCX]-positive cells were specifically observed in the DG, but not the SVZ/RMS/MOB neurogenic region, of Ras-GRF2-KO and Ras-GRF1/2-DKO mice indicating that this novel Ras-GRF2-dependent phenotype is spatially restricted to a specific neurogenic area. Consistent with a role of CREB as mediator of Ras-GRF2 function in neurogenesis, the density of p-CREB-positive cells was also specifically reduced in all neurogenic regions of Ras-GRF2-KO and DKO mice. Similar levels of early neurogenic proliferation markers (Ki67, BrdU) were observed in all different Ras-GRF genotypes analyzed but significantly elevated levels of nestin-immunolabel, particularly of undifferentiated, highly ramified, A-type nestin-positive neurons were specifically detected in the DG but not the SVZ/RMS/MOB of Ras-GRF2-KO and DKO mice. Together with assays of other neurogenic markers (GFAP, Sox2, Tuj1, NeuN), these observations suggest that the deficit of DCX/p-CREB-positive cells in the DG of Ras-GRF2-depleted mice does not involve impaired neuronal proliferation but rather delayed transition from the stem cell stage to the differentiation stages of the neurogenic process. This model is also supported by functional analyses of DG-derived neurosphere cultures and transcriptional characterization of the neurogenic areas of mice of all relevant Ras-GRF genotypes suggesting that the neurogenic role of Ras-GRF2 is exerted in a cell-autonomous manner through a specific transcriptional program. eng Attribution-NonCommercial-NoDerivatives 4.0 Internacional Adult Neurogenesis Dentate Gyrus Ras-GEF Neural Stem Cell Ras-GRF2 regulates nestin-positive stem cell density and onset of differentiation during adult neurogenesis in the mouse dentate gyrus info:eu-repo/semantics/article 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 URL https://gredos.usal.es/bitstream/10366/169690/1/Gomez%20et%20al%202017_Mol%20and%20Cell%20Neurosci.pdf File MD5 49fd9774528210286178e17f1fc4f921 2528015 application/pdf Gomez et al 2017_Mol and Cell Neurosci.pdf URL https://gredos.usal.es/bitstream/10366/169690/4/Gomez%20et%20al%202017_Mol%20and%20Cell%20Neurosci.pdf.txt File MD5 c9f665d4541e860d9c2bfae7362f6f10 142591 text/plain Gomez et al 2017_Mol and Cell Neurosci.pdf.txt