Wakabayashi Tamami, Hidaka Ryo, Fujimaki Shin, Asashima Makoto, Kuwabara Tomoko
Research Center for Stem Cell Engineering, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba Science City, Ibaraki, Japan; Physical Education, Health and Sport Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan.
Adv Genet. 2014;86:27-44. doi: 10.1016/B978-0-12-800222-3.00002-4.
Neurogenesis occurs throughout adulthood in the mammalian brain. Neural stem cells (NSCs) exist in three distinct areas of the brain: the subventricular zone, the olfactory bulb, and the dentate gyrus of the hippocampus. MicroRNAs (miRNAs) are small noncoding RNA molecules that posttranscriptionally regulate gene expression. Epigenetic regulation of gene expression, which includes DNA methylation and histone modification, plays a significant role in modulating NSC proliferation and differentiation. However, the functions of miRNAs in neurogenesis are just beginning to be understood. Based on the recent literature, miRNAs are suggested to play an important role in the epigenetic regulation of NSCs and differentiation of lineage populations, which include neurons, astrocytes, and oligodendrocytes. Recent studies have elucidated the roles of miRNAs in embryonic and adult neurogenesis, specifically, their involvement in stem cell maintenance and differentiation, neuronal maturation and neurite outgrowth, dendritogenesis, and spine formation. The cross-talk between miRNAs and epigenetic regulators appears to modulate neurogenesis in the adult mammalian brain. Since the dysfunction in miRNA machinery contributes to many types of neurodegenerative disorders, a better understanding of how miRNAs influence the neurogenesis and differentiation may offer novel targets for therapeutic application.
神经发生在成年哺乳动物大脑中贯穿始终。神经干细胞(NSCs)存在于大脑的三个不同区域:脑室下区、嗅球和海马体的齿状回。微小RNA(miRNAs)是小的非编码RNA分子,可在转录后调节基因表达。基因表达的表观遗传调控,包括DNA甲基化和组蛋白修饰,在调节神经干细胞的增殖和分化中起重要作用。然而,miRNAs在神经发生中的功能才刚刚开始被了解。基于最近的文献,miRNAs被认为在神经干细胞的表观遗传调控和谱系群体(包括神经元、星形胶质细胞和少突胶质细胞)的分化中起重要作用。最近的研究阐明了miRNAs在胚胎和成年神经发生中的作用,特别是它们在干细胞维持和分化、神经元成熟和神经突生长、树突形成和棘突形成中的参与。miRNAs与表观遗传调节因子之间的相互作用似乎调节成年哺乳动物大脑中的神经发生。由于miRNA机制的功能障碍会导致多种神经退行性疾病,更好地了解miRNAs如何影响神经发生和分化可能为治疗应用提供新的靶点。