J. Zhang, J. Zhang, Y. Zhou, Y. -J. Wu, L. Ma, R. -J. Wang, S. -Q. Huang, R. -R. Gao, L. -H. Liu, Z. -H. Shao, H. -J. Shi, L. -M. Cheng and L. Yu Pages 1432 - 1445 ( 14 )
MicroRNAs (miRNAs) are a class of small non-encoding RNAs that regulate gene expression at the posttranscriptional level. MiRNAs may characterize not only specific stages of the development of the neural cell population in CNS, but also distinct types of neural cells. However, the common pathways of the neural enriched miRNAs involved in neurogenesis of specific cell lineages remain poorly understood. In this report, in order to get insights into the common role of the miRNAs shared by cerebellum and forebrain, we studied the regulatory mechanism of neural enriched-miRNA in neural progenitor cell (NPCs) differentiation. Here, we identified a new cerebellum-enriched rno-miR-592 in rat cerebellum. It showed that rno-miR-592 was a neuralenriched miRNA and may play an important role in rat embryonic neurogenesis or/and astrogliogenesis. We used both gain-of -function and loss-of -function approaches to demonstrate that rno-miR-592 could change the balance between neuron- and astrocyte- like differentiation and neuronal morphology. We observed that miR-592 could induce astrogliogenesis differentiation arrest or/and enhance neurogenesis in vitro. Meanwhile, silencing of miR-592 was not beneficial for neuronal maturation. We also identified Lrrc4c and Nfasc as miR- 592 target genes, and miR-592 could affect the changes of Lrrc4c and Nfasc expression levels, suggesting that these two target genes may be involved in miR-592 regulative function in NPCs differentiation and neuronal maturation. Thus, we conclude that rno-miR-592 may affect the neural lineage differentiation via reducing astrogliogenesis or/and enhancing neurogenesis at least in part through regulating its target genes Lrrc4c and Nfasc in vitro. Together, we report here for the first time the important role of miR-592 in rat NPCs differentiation and neuronal maturation.
Cerebellum, differentiation, Lrrc4c, miR-592, Nfasc, NPCs, neurogenesis.
Department of Regenerative Medicine, Tongji University School of Medicine, 1239 Siping Road, Shanghai 200092, P.R. China.