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Major signaling pathways in migrating neuroblasts.

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.

SUBMITTER: Khodosevich K

PROVIDER: S-EPMC2724029 | biostudies-literature | 2009

REPOSITORIES: biostudies-literature

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Major signaling pathways in migrating neuroblasts.

Khodosevich Konstantin K Seeburg Peter H PH Monyer Hannah H

Frontiers in molecular neuroscience 20090724

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 ...[more]

PMID: 19668709

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Project description:New neurons, referred to as neuroblasts, are continuously generated in the ventricular-subventricular zone of the brain throughout an animal's life. These neuroblasts are characterized by their unique potential for proliferation, formation of chain-like cell aggregates, and long-distance and high-speed migration through the rostral migratory stream (RMS) toward the olfactory bulb (OB), where they decelerate and differentiate into mature interneurons. The dynamic changes of ultrastructural features in postnatal-born neuroblasts during migration are not yet fully understood. Here we report the presence of a primary cilium, and its ultrastructural morphology and spatiotemporal dynamics, in migrating neuroblasts in the postnatal RMS and OB. The primary cilium was observed in migrating neuroblasts in the postnatal RMS and OB in male and female mice and zebrafish, and a male rhesus monkey. Inhibition of intraflagellar transport molecules in migrating neuroblasts impaired their ciliogenesis and rostral migration toward the OB. Serial section transmission electron microscopy revealed that each migrating neuroblast possesses either a pair of centrioles or a basal body with an immature or mature primary cilium. Using immunohistochemistry, live imaging, and serial block-face scanning electron microscopy, we demonstrate that the localization and orientation of the primary cilium are altered depending on the mitotic state, saltatory migration, and deceleration of neuroblasts. Together, our results highlight a close mutual relationship between spatiotemporal regulation of the primary cilium and efficient chain migration of neuroblasts in the postnatal brain.SIGNIFICANCE STATEMENT Immature neurons (neuroblasts) generated in the postnatal brain have a mitotic potential and migrate in chain-like cell aggregates toward the olfactory bulb. Here we report that migrating neuroblasts possess a tiny cellular protrusion called a primary cilium. Immunohistochemical studies with zebrafish, mouse, and monkey brains suggest that the presence of the primary cilium in migrating neuroblasts is evolutionarily conserved. Ciliogenesis in migrating neuroblasts in the rostral migratory stream is suppressed during mitosis and promoted after cell cycle exit. Moreover, live imaging and 3D electron microscopy revealed that ciliary localization and orientation change during saltatory movement of neuroblasts. Our results reveal highly organized dynamics in maturation and positioning of the primary cilium during neuroblast migration that underlie saltatory movement of postnatal-born neuroblasts.

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Major signaling pathways in migrating neuroblasts.

Publications

Major signaling pathways in migrating neuroblasts.

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