microRNA-124 regulates Notch and NeuroD1 to mediate transition states of neuronal development.

microRNA-124 regulates Notch and NeuroD1 to mediate transition states of neuronal development.
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DOI:
10.1002/dneu.22902
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发表时间:
2023-01
影响因子:
3
通讯作者:
--
中科院分区:
医学3区
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--
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MicroRNA 通过破坏动物细胞中靶 mRNA 的稳定性和/或抑制翻译来调节基因表达。在单个系统内发育过程中神经元的规范、分化和成熟过程中机械剖析 miR-124 功能的能力尚未实现。使用海胆胚胎,我们利用了胚胎的可操作性及其有据可查的基因调控网络(GRN)。我们将 NeuroD1 作为海胆神经元 GRN 的一部分,并确定 miR-124 抑制会导致异常的肠道收缩、游泳速度和神经元发育。抑制 miR-124 导致表达与祖神经元相关的转录因子 (TF) 的细胞数量增加,同时成熟和功能神经元的减少。结果显示,在早期囊胚/原肠胚阶段,miR-124 在神经元规范和分化过程中调节未定义的因素。在原肠胚晚期/幼虫阶段,miR-124 在神经元分化和成熟之间的过渡期间调节 Notch 和 NeuroD1。总体而言,我们改进了神经元 GRN,并确定 miR-124 在调节神经元发育的各种转变中发挥着重要作用。
MicroRNAs regulate gene expression by destabilizing target mRNA and/or inhibiting translation in animal cells. The ability to mechanistically dissect miR-124′s function during specification, differentiation, and maturation of neurons during development within a single system has not been accomplished. Using the sea urchin embryo, we take advantage of the manipulability of the embryo and its well-documented gene regulatory networks (GRNs). We incorporated NeuroD1 as part of the sea urchin neuronal GRN and determined that miR-124 inhibition resulted in aberrant gut contractions, swimming velocity, and neuronal development. Inhibition of miR-124 resulted in an increased number of cells expressing transcription factors (TFs) associated with progenitor neurons and a concurrent decrease of mature and functional neurons. Results revealed that in the early blastula/gastrula stages, miR-124 regulates undefined factors during neuronal specification and differentiation. In the late gastrula/larval stages, miR-124 regulates Notch and NeuroD1 during the transition between neuronal differentiation and maturation. Overall, we have improved the neuronal GRN and identified miR-124 to play a prolific role in regulating various transitions of neuronal development.
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