The State Key Laboratory of Medical Molecular Biology, Neuroscience Center, Medical Primates Research Center and Department of Molecular Biology and Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100005, China.
Department of Anatomy and Histology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100005, China.
Sci Rep. 2017 Aug 14;7(1):8014. doi: 10.1038/s41598-017-08450-8.
The accurate generation of an appropriate number of different neuronal and glial subtypes is fundamental to normal brain functions and requires tightly orchestrated spatial and temporal developmental programmes to maintain the balance between the proliferation and the differentiation of neural progenitor cells. However, the molecular mechanism governing this process has not been fully elucidated. Here, we found that miR-214-3p was highly expressed in neural progenitor cells and dynamically regulated during neocortical development. Moreover, our in vivo and in vitro studies showed that miR-214 inhibited self-renewal of neural progenitor cells and promoted neurogenesis. In addition, after target screening, we identified miR-214 targets including Quaking (Qki) by binding the 3'- untranslated region (3'-UTR) of the Qki mRNA, which was specifically expressed in the progenitor cells of the proliferative ventricular zone as 3 Qki isoforms. Furthermore, overexpression and knockdown of Qki showed that the different isoforms of Qki had different functions in the regulation of neural progenitor cells differentiation. Moreover, overexpression of Qki could counteract the function of miR-214 in neurogenesis. Our results revealed that miR-214 maintains the balance between neural progenitor/stem cell proliferation and differentiation together with Quaking, its target gene.
准确产生不同数量和类型的神经元和神经胶质细胞对于大脑的正常功能至关重要，这需要通过严格协调的时空发育程序来维持神经祖细胞的增殖和分化之间的平衡。然而，调控这一过程的分子机制尚未完全阐明。在这里，我们发现 miR-214-3p 在神经祖细胞中高度表达，并在大脑皮质发育过程中动态调节。此外，我们的体内和体外研究表明，miR-214 抑制神经祖细胞的自我更新并促进神经发生。此外，通过靶标筛选，我们鉴定了 miR-214 的靶标，包括 QKI（Quaking），通过结合 QKI mRNA 的 3'-UTR（非翻译区），其特异性在增殖室带的祖细胞中表达为 3 种 QKI 异构体。此外，QKI 的过表达和敲低表明，QKI 的不同异构体在调节神经祖细胞分化方面具有不同的功能。此外，QKI 的过表达可以抵消 miR-214 在神经发生中的作用。我们的研究结果表明，miR-214 与靶基因 Quaking 一起维持神经祖细胞/干细胞增殖和分化之间的平衡。
