Birdsong decreases protein levels of FoxP2, a molecule required for human speech
Birdsong decreases protein levels of FoxP2, a molecule required for human speech
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DOI：
10.1152/jn.90415.2008
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发表时间：
2008-10-01
影响因子：
2.5
通讯作者：
White, Stephanie A.
中科院分区：
文献类型：
--
作者：
Miller, Julie E.;Spiteri, Elizabeth;White, Stephanie A.
与语言和言语相关的认知和运动缺陷在携带FOXP2突变的人类中被发现。FOXP2突变相关缺陷的神经基础被认为存在于结构异常中，这些结构异常分布在对语言和运动学习至关重要的系统中，包括大脑皮层、基底节和小脑。在这些大脑区域，我们之前的研究表明，在发育中的人类和鸣禽之间，FoxP2 mRNA的表达模式惊人地相似。在鸣禽的大脑中，这种模式贯穿一生，并包括纹状体亚区，即致力于鸣叫发育和维持的X区。这种持续的mRNA表达表明，FoxP2的作用超出了发声学习回路的形成，并持续使用。由于FoxP2是一种转录因子，在形成电路中的作用可能取决于FoxP2蛋白水平，而FoxP2蛋白水平可能并不总是与mRNA水平平行。事实上，我们目前的研究表明，当成年男性唱歌时，FoxP2蛋白和它的mRNA一样，在成熟的X区急剧下调。与不同行为背景相关的总皮质酮水平没有变化，这表明FoxP2水平的差异不太可能归因于压力。我们的数据和最近关于FOXP2的S靶基因的报道表明，FOXP2水平的降低可能允许对电路修饰至关重要的基因的表达，从而导致声音的可变性。
Cognitive and motor deficits associated with language and speech are seen in humans harboring FOXP2 mutations. The neural bases for FOXP2 mutation-related deficits are thought to reside in structural abnormalities distributed across systems important for language and motor learning including the cerebral cortex, basal ganglia, and cerebellum. In these brain regions, our prior research showed that FoxP2 mRNA expression patterns are strikingly similar between developing humans and songbirds. Within the songbird brain, this pattern persists throughout life and includes the striatal subregion, Area X, that is dedicated to song development and maintenance. The persistent mRNA expression suggests a role for FoxP2 that extends beyond the formation of vocal learning circuits to their ongoing use. Because FoxP2 is a transcription factor, a role in shaping circuits likely depends on FoxP2 protein levels which might not always parallel mRNA levels. Indeed our current study shows that FoxP2 protein, like its mRNA, is acutely downregulated in mature Area X when adult males sing with some differences. Total corticosterone levels associated with the different behavioral contexts did not vary, indicating that differences in FoxP2 levels are not likely attributable to stress. Our data, together with recent reports on FoxP2's target genes, suggest that lowered FoxP2 levels may allow for expression of genes important for circuit modification and thus vocal variability.