Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University School of Life Sciences, China.
FEBS J. 2014 Feb;281(4):1144-58. doi: 10.1111/febs.12680. Epub 2014 Jan 15.
MicroRNAs (miRNAs) are endogenously expressed small, non-coding nucleotides that repress gene expression at the post-transcriptional level. In mammals, the developing brain contains a large, diverse group of miRNAs, which suggests that they play crucial roles in neural development. In the present study, we analyzed the miRNA expression patterns in the mouse cortex at various developmental stages. We found that miR-17 family miRNAs were highly expressed in the cortex during early developmental stages, and that their expression levels gradually decreased as the cortex developed. Further investigation revealed that the change in miR-17-5p expression occurred in the ventricular zone/sub-ventricular zone. In addition to promoting cell proliferation, miR-17-5p also influences the differentiation fate of neural precursor cells exposed to bone morphogenetic protein 2. Moreover, we show that these effects of miR-17-5p were mainly the result of regulating the bone morphogenetic protein signaling pathway by repressing expression of the bone morphogenetic protein type II receptor. Taken together, these findings suggest that miR-17 family members play a pivotal role in regulating cell activity during early development of the mouse cortex.
微小 RNA(miRNAs)是内源性表达的小的非编码核苷酸,在转录后水平抑制基因表达。在哺乳动物中,发育中的大脑包含大量不同的 miRNAs,这表明它们在神经发育中发挥着关键作用。在本研究中,我们分析了不同发育阶段小鼠皮层中的 miRNA 表达模式。我们发现 miR-17 家族 miRNAs 在早期发育阶段在皮层中高度表达,并且随着皮层的发育,其表达水平逐渐降低。进一步的研究表明,miR-17-5p 的表达变化发生在脑室区/下脑室区。miR-17-5p 除了促进细胞增殖外,还影响暴露于骨形态发生蛋白 2 的神经前体细胞的分化命运。此外,我们表明,miR-17-5p 的这些作用主要是通过抑制骨形态发生蛋白 II 型受体的表达来调节骨形态发生蛋白信号通路。总之,这些发现表明 miR-17 家族成员在调节小鼠皮层早期发育过程中的细胞活性方面发挥着关键作用。