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首页> 外文期刊>The Journal of Neuroscience: The Official Journal of the Society for Neuroscience >miR-9 and miR-140-5p target FoxP2 and are regulated as a function of the social context of singing behavior in zebra finches
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miR-9 and miR-140-5p target FoxP2 and are regulated as a function of the social context of singing behavior in zebra finches

机译：miR-9和miR-140-5p以FoxP2为靶标，并根据斑马雀的唱歌行为的社交情境进行调节

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Mutations in the FOXP2 gene cause speech and language impairments, accompanied by structural and functional abnormalities in brain regions underlying speech-related sensory-motor processing, including the striatum and cerebellum. The sequence and expression patterns of FOXP2 are highly conserved among higher vertebrates. In the zebra finch brain, FoxP2 is expressed in Area X, a striatal nucleus required for vocal learning, and reduced FoxP2 expression impairs dendritic development and vocal learning. The FoxP2 gene encodes a transcription factor that controls the expression of many downstream genes. However, how FOXP2 gene expression is regulated is not clearly understood. miRNAs regulate gene expression post-transcriptionally by targeting the 3′-untranslated regions (UTRs) of mRNAs, leading to translational suppression or mRNA degradation. In this study, we identified miR-9 and miR-140-5p as potential regulators of the FoxP2 gene. We show that both miR-9 and miR-140-5p target specific sequences in the FoxP2 3′-UTR and downregulate FoxP2 protein and mRNA expression in vitro. We also show that the expression of miR-9 and miR-140-5p in Area X of the zebra finch brain is regulated during song development in juvenile zebra finches. We further show that in adult zebra finches the expression of miR-9 and miR-140-5p in Area X is regulated as a function of the social context of song behavior in males singing undirected songs. Our findings reveal a post-transcriptional mechanism that regulates FoxP2 expression and suggest that social vocal behavior can influence the basal ganglia circuit controlling vocal learning via a miRNA-FoxP2 gene regulatory network.
机译：FOXP2基因的突变会导致语音和语言障碍，并伴随与语音有关的感觉运动处理（包括纹状体和小脑）的大脑区域出现结构和功能异常。 FOXP2的序列和表达模式在高等脊椎动物中高度保守。在斑马雀科的大脑中，FoxP2在区域X中表达，区域X是发声学习所需的纹状体核，而FoxP2表达的降低会损害树突的发育和发声学习。 FoxP2基因编码控制许多下游基因表达的转录因子。但是，尚不清楚如何调节FOXP2基因表达。 miRNA通过靶向mRNA的3'-非翻译区（UTR）转录后调节基因表达，从而导致翻译抑制或mRNA降解。在这项研究中，我们确定了miR-9和miR-140-5p是FoxP2基因的潜在调控因子。我们显示，miR-9和miR-140-5p均靶向FoxP2 3'-UTR中的特定序列，并在体外下调FoxP2蛋白和mRNA表达。我们还显示，在青少年斑马雀科的歌曲发育过程中，调节斑马雀科大脑X区中miR-9和miR-140-5p的表达。我们进一步表明，在成年斑马雀中，miR-9和miR-140-5p在X区域的表达被调节为男性无定向歌唱行为的社会背景。我们的发现揭示了调节FoxP2表达的转录后机制，并表明社交声音行为可以影响通过miRNA-FoxP2基因调控网络控制神经元学习的基底神经节回路。

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