MiR-124-regulated RhoG During Olfactory Bulb Neuronal Differentiation

The olfactory system has important significance for the animals to find food,identify hazards and mates and social communication.Olfactory bub(OB)intemeurons are continuously renewed in mammalian brain.The adult subventricular zone(SVZ)is one of two neurogenic zones in the adult brain of mammalian specie.Neuroblasts from the SVZ migrate along a rostral migratory stream(RMS)into the OB and differentiate into granule cells(GCS)and periglomerular cells(PGCS)which then integrate into the synaptic circuits of the OB.Granule cells are inhibitory neurons,composed of 95%interneuron in olfactory bulb.They are axonless,extend short basal dendrites in the GCL,and project along apical spiny dendrite that crosses the mitral cell body layer(MCL)and makes numerous branches in the external plexiform layer(EPL).MicroRNAs are Small ncRNAs,short single-stranded RNA,the length of the molecule is 18-25 nucleotides.microRNA molecule is a major regulator of post-transcriptional gene expression.microRNA sequence complementary to bind target mRNA,by degrading or inhibiting the target gene mRNA translational with regulation of the expression of its target gene protein.microRNA play an important role in neuronal development and central nervous system disorders.miR-124 is a brain-specific miRNA.Accounting for 25-48%of all brain miRNA in mouse brain differentiation and maturation of neurons.miR-124 expression levels in the developing mouse central nervous system(CNS)is gradually increased.miR-124 is a Subventric?lar Zone Neuronal Fate Determinant and regulate adult neurogenesis in the SVZ.miR-124 have important function in regulating neuronal development and play an important role in neurodegenerative diseases.Small G proteins(Small G Protein),due to the molecular weight of only 20?30KD named,is located inside the membrane of a class of conjugated proteins,by binding to the membrane receptor cytoplasmic domain,the membrane receptor and ligand binding stimulus and downstream effector molecules coupled together.Rho GTPases family actin cytoskeleton by modulating muscle occurs important role in dendritic spine morphology and synaptic plasticity of brain neurons.Reveal the olfactory bulb miRNA expression profiling,by miRNA chip method.We find miR-124 was the highest expression of the olfactory bulb.Through target gene prediction and functional networks enrichment,we get miR-124 involved in the regulation of cytoskeletal important functions.By building miR-124 overexpression and inhibition of lentiviral vectors by stereotaxic injection into the RMS mice,we show that miR-124 in the late developmental regulation of mouse olfactory bulb granule cells and dendritic morphogenesis of dendritic spine density.in the cytoskeletal component-enriched target genes,we found that small G proteins RhoG may have an important role.We constructed RhoG overexpression vector,RhoG of constitutively activating mutations,RhoG constitutive inactivation carrier and RhoG of shRNA lentiviral vectors.By stereotaxic injection into the RMS mice,we show that RhoG promote olfactory bulb granule cells and dendritic morphogenesis of dendritic spine density.RhoG play a role through the downstream of Racl activation and phosphorylation of PAK and confilin.Although the expression pattern of RhoG is very similar with RhoG.This seemingly contradictory,RhoG have function in regulating migration of neuroblast.RhoG may play a role in regulating neuroblast migration from the SVZ to the olfactory bulb.This function is tightly regulated miR-124.So presumably miR-124 involved in the regulation RhoG appropriate developmental level of the olfactory bulb granule cells.