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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >A molecular neuroethological approach for identifying and characterizing a cascade of behaviorally regulated genes
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A molecular neuroethological approach for identifying and characterizing a cascade of behaviorally regulated genes

机译：鉴定和表征一系列行为调控基因的分子神经伦理学方法

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摘要

Songbirds have one of the most accessible neural systems for the study of brain mechanisms of behavior. However, neuroethological studies in songbirds have been limited by the lack of high-throughput molecular resources and gene-manipulation tools. To overcome these limitations, we constructed 21 regular, normalized, and subtracted full-length cDNA libraries from brains of zebra finches in 57 developmental and behavioral conditions in an attempt to clone as much of the brain transcriptome as possible. From these libraries, ≈14,000 transcripts were isolated, representing an estimated 4,738 genes. With the cDNAs, we created a hierarchically organized transcriptome database and a large-scale songbird brain cDNA microarray. We used the arrays to reveal a set of 33 genes that are regulated in forebrain vocal nuclei by singing behavior. These genes clustered into four anatomical and six temporal expression patterns. Their functions spanned a large range of cellular and molecular categories, from signal transduc-tion, trafficking, and structural, to synaptically released molecules. With the full-length cDNAs and a lentiviral vector system, we were able to overexpress, in vocal nuclei, proteins of representative singing-regulated genes in the absence of singing.
机译：鸣禽具有研究大脑行为机制的最容易接近的神经系统之一。但是，由于缺乏高通量分子资源和基因操纵工具，对鸣禽的神经行为学研究受到了限制。为了克服这些限制，我们在57种发育和行为条件下从斑马雀科的大脑中构建了21个规则的，标准化的和减去的全长cDNA文库，以尝试克隆尽可能多的大脑转录组。从这些文库中，分离出约14,000个转录本，代表估计的4,738个基因。利用这些cDNA，我们创建了一个层次化的转录组数据库和一个大型的鸣禽脑cDNA微阵列。我们使用这些阵列揭示了一组33种基因，这些基因通过唱歌行为在前脑声带中得到调节。这些基因聚集成四个解剖结构和六个时间表达模式。它们的功能涵盖了广泛的细胞和分子类别，从信号转导，运输和结构到突触释放的分子。有了全长cDNA和慢病毒载体系统，我们能够在没有唱歌的情况下在声带中过表达代表性歌唱调节基因的蛋白质。

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