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RMS neuronal migration, microarray analysis, SVZ, signaling pathways, in vivo gene silencing
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 fi nal 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 fi nal destination, the olfactory bulb (OB). We identifi ed 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 specifi c upregulated intracellular
network, the cytoskeleton pathway, we confi rmed by functional in vitro and in vivo analysis that
the identifi ed 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
