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Major signaling pathways in migrating neuroblasts.

Khodosevich K, Seeburg PH, Monyer H - Front Mol Neurosci (2009)

Bottom Line: We compared gene expression patterns of neuroblasts obtained from two sites of the RMS, one closer to the site of origin, the subventricular zone, and one closer to the site of the final destination, the olfactory bulb (OB).Based on the validity of this approach, we chose four new networks and tested by functional in vivo analysis their involvement in neuroblast migration.Thus, knockdown of Calm1, Gria1 (GluA1) and Camk4 (calmodulin-signaling network), Hdac2 and Hsbp1 (Akt1-DNA transcription network), Vav3 and Ppm1a (growth factor signaling network) affected neuroblast migration to the OB.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Neurobiology, Interdisciplinary Center for Neurosciences Heidelberg, Germany.

ABSTRACT
Neuronal migration is a key process in the developing and adult brain. Numerous factors act on intracellular cascades of migrating neurons and regulate the final position of neurons. One robust migration route persists postnatally - the rostral migratory stream (RMS). To identify genes that govern neuronal migration in this unique structure, we isolated RMS neuroblasts by making use of transgenic mice that express EGFP in this cell population and performed microarray analysis on RNA. We compared gene expression patterns of neuroblasts obtained from two sites of the RMS, one closer to the site of origin, the subventricular zone, and one closer to the site of the final destination, the olfactory bulb (OB). We identified more than 400 upregulated genes, many of which were not known to be involved in migration. These genes were grouped into functional networks by bioinformatics analysis. Selecting a specific upregulated intracellular network, the cytoskeleton pathway, we confirmed by functional in vitro and in vivo analysis that the identified genes of this network affected RMS neuroblast migration. Based on the validity of this approach, we chose four new networks and tested by functional in vivo analysis their involvement in neuroblast migration. Thus, knockdown of Calm1, Gria1 (GluA1) and Camk4 (calmodulin-signaling network), Hdac2 and Hsbp1 (Akt1-DNA transcription network), Vav3 and Ppm1a (growth factor signaling network) affected neuroblast migration to the OB.

No MeSH data available.


Effect of in vivo gene expression knockdown on neuroblast migration in the olfactory bulb. The RMS within the olfactory bulb (bRMS) is visible as more intensely stained in the panels showing doublecortin (DCX) expression thus clearly delineating it from the more lightly stained granule cell layer (GCL). In comparison to control shRNAScrambled (A), Calm1 (B) or Hdac2 (C) gene knockdown resulted in fewer cells in the GCL but more cells in the bRMS relative to the whole OB 4 days post-injection. (D) Percentage of green fluorescent cells in the bRMS (more intensive red area) to green fluorescent cells in the whole OB in control and gene knockdown experiments (*p < 0.01).
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Figure 7: Effect of in vivo gene expression knockdown on neuroblast migration in the olfactory bulb. The RMS within the olfactory bulb (bRMS) is visible as more intensely stained in the panels showing doublecortin (DCX) expression thus clearly delineating it from the more lightly stained granule cell layer (GCL). In comparison to control shRNAScrambled (A), Calm1 (B) or Hdac2 (C) gene knockdown resulted in fewer cells in the GCL but more cells in the bRMS relative to the whole OB 4 days post-injection. (D) Percentage of green fluorescent cells in the bRMS (more intensive red area) to green fluorescent cells in the whole OB in control and gene knockdown experiments (*p < 0.01).

Mentions: A striking effect was visible when restricting the analysis to the bulb and quantifying the ratio of tangential versus radial migration. Thus, in animals with Calm1/Camk4 knockdown, the number of infected neuroblasts in the part of the RMS within the OB (tangentially migrating cells) was increased with a concomitant decreased number of labeled cells outside of the stream (radially migrating cells) (Figures 7A,B,D).


Major signaling pathways in migrating neuroblasts.

Khodosevich K, Seeburg PH, Monyer H - Front Mol Neurosci (2009)

Effect of in vivo gene expression knockdown on neuroblast migration in the olfactory bulb. The RMS within the olfactory bulb (bRMS) is visible as more intensely stained in the panels showing doublecortin (DCX) expression thus clearly delineating it from the more lightly stained granule cell layer (GCL). In comparison to control shRNAScrambled (A), Calm1 (B) or Hdac2 (C) gene knockdown resulted in fewer cells in the GCL but more cells in the bRMS relative to the whole OB 4 days post-injection. (D) Percentage of green fluorescent cells in the bRMS (more intensive red area) to green fluorescent cells in the whole OB in control and gene knockdown experiments (*p < 0.01).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2724029&req=5

Figure 7: Effect of in vivo gene expression knockdown on neuroblast migration in the olfactory bulb. The RMS within the olfactory bulb (bRMS) is visible as more intensely stained in the panels showing doublecortin (DCX) expression thus clearly delineating it from the more lightly stained granule cell layer (GCL). In comparison to control shRNAScrambled (A), Calm1 (B) or Hdac2 (C) gene knockdown resulted in fewer cells in the GCL but more cells in the bRMS relative to the whole OB 4 days post-injection. (D) Percentage of green fluorescent cells in the bRMS (more intensive red area) to green fluorescent cells in the whole OB in control and gene knockdown experiments (*p < 0.01).
Mentions: A striking effect was visible when restricting the analysis to the bulb and quantifying the ratio of tangential versus radial migration. Thus, in animals with Calm1/Camk4 knockdown, the number of infected neuroblasts in the part of the RMS within the OB (tangentially migrating cells) was increased with a concomitant decreased number of labeled cells outside of the stream (radially migrating cells) (Figures 7A,B,D).

Bottom Line: We compared gene expression patterns of neuroblasts obtained from two sites of the RMS, one closer to the site of origin, the subventricular zone, and one closer to the site of the final destination, the olfactory bulb (OB).Based on the validity of this approach, we chose four new networks and tested by functional in vivo analysis their involvement in neuroblast migration.Thus, knockdown of Calm1, Gria1 (GluA1) and Camk4 (calmodulin-signaling network), Hdac2 and Hsbp1 (Akt1-DNA transcription network), Vav3 and Ppm1a (growth factor signaling network) affected neuroblast migration to the OB.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Neurobiology, Interdisciplinary Center for Neurosciences Heidelberg, Germany.

ABSTRACT
Neuronal migration is a key process in the developing and adult brain. Numerous factors act on intracellular cascades of migrating neurons and regulate the final position of neurons. One robust migration route persists postnatally - the rostral migratory stream (RMS). To identify genes that govern neuronal migration in this unique structure, we isolated RMS neuroblasts by making use of transgenic mice that express EGFP in this cell population and performed microarray analysis on RNA. We compared gene expression patterns of neuroblasts obtained from two sites of the RMS, one closer to the site of origin, the subventricular zone, and one closer to the site of the final destination, the olfactory bulb (OB). We identified more than 400 upregulated genes, many of which were not known to be involved in migration. These genes were grouped into functional networks by bioinformatics analysis. Selecting a specific upregulated intracellular network, the cytoskeleton pathway, we confirmed by functional in vitro and in vivo analysis that the identified genes of this network affected RMS neuroblast migration. Based on the validity of this approach, we chose four new networks and tested by functional in vivo analysis their involvement in neuroblast migration. Thus, knockdown of Calm1, Gria1 (GluA1) and Camk4 (calmodulin-signaling network), Hdac2 and Hsbp1 (Akt1-DNA transcription network), Vav3 and Ppm1a (growth factor signaling network) affected neuroblast migration to the OB.

No MeSH data available.