miR-9*- and miR-124a-Mediated Switching of Chromatin Remodelling Complexes is Altered in Rat Spina Bifida Aperta
miR-9*- and miR-124a-Mediated Switching of Chromatin Remodelling Complexes is Altered in Rat Spina Bifida Aperta
复制标题
miR-9* 和 miR-124a 介导的染色质重塑复合物转换在大鼠脊柱裂中发生改变
DOI：
10.1007/s11064-013-1062-8
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发表时间：
2013-08-01
影响因子：
4.4
通讯作者：
Yuan, Zhengwei
中科院分区：
文献类型：
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作者：
Wei, Xiaowei;Li, Hui;Yuan, Zhengwei
神经管缺损是一种复杂的先天性畸形，是由神经发育不全引起的。我们之前的工作已经证明，运动和感觉神经元发育缺陷的大鼠胚胎与脊柱裂。为了确定神经发育相关的mirna是否在NTDs的神经功能缺陷中发挥作用，我们筛选了一组神经发育相关的mirna，包括miR-9、miR-9*、miR-124a、miR-10a、miR10b、miR-34a、miR-221和miR-222，这些mirna存在于视黄酸诱导的大鼠脊髓中。我们发现，与没有脊柱裂的脊髓相比，miR-9、miR-9*和miR-124a的表达特异性下调。为了进一步阐明miR-9*和miR-124a的下调是否会导致NTDs的神经功能缺陷，我们研究了参与miR-9*和miR-124a调节的Swi/ snf样BAF （Brg/Brm相关因子）复合物亚基组成转换和神经元分化的基因水平。除了miR-9*和miR-124a表达下调外，我们还观察到抑制元件沉默转录因子（REST）和BAF53a的表达增加，BAF53b、Brg1和NeuroD1的表达降低。我们的研究结果表明，rest调控的miR-9*-和mir -124a介导的染色质重塑调控机制可能参与了脊柱裂的神经元缺陷。
Neural tube defects (NTDs) are complex congenital malformations resulting from incomplete neurulation. Our previous work has demonstrated that motor and sensory neurons develop defectively in rat embryos with spina bifida aperta. To identify whether neural development-associated miRNAs play a role in the neurological deficits of NTDs, we screened a panel of neural development-related miRNAs, including miR-9, miR-9*, miR-124a, miR-10a, miR10b, miR-34a, miR-221 and miR-222, in the spinal cords of rats with retinoic acid-induced spina bifida aperta. We discovered that the expression of miR-9, miR-9* and miR-124a was specifically down-regulated compared to spinal cords without spina bifida. To further clarify whether down-regulation of miR-9* and miR-124a contributes to the neurological deficits of NTDs, we investigated the levels of genes involved in switching in the subunit composition of Swi/Snf-like BAF (Brg/Brm associated factor) complexes modulated by miR-9* and miR-124a and neuronal differentiation. In addition to the down-regulation of miR-9* and miR-124a expression, we also observed increased expression of repressor element silencing transcription factor (REST) and BAF53a and decreased expression of BAF53b, Brg1 and NeuroD1. Our results suggest that REST-regulated miR-9*- and the miR-124a-mediated chromatin remodelling regulatory mechanism may participate in the neuronal deficits of spina bifida.