FoxP2 isoforms delineate spatiotemporal transcriptional networks for vocal learning in the zebra finch.
FoxP2 isoforms delineate spatiotemporal transcriptional networks for vocal learning in the zebra finch.
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DOI：
10.7554/elife.30649
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发表时间：
2018-01-23
期刊：
影响因子：
7.7
通讯作者：
White SA
中科院分区：
文献类型：
--
作者：
Burkett ZD;Day NF;Kimball TH;Aamodt CM;Heston JB;Hilliard AT;Xiao X;White SA
人类的语音是哺乳动物学习发声的为数不多的例子之一，然而，有一半的鸟类表现出这种能力。除了人类和斑马雀对FoxP2的共同需求外，它的神经遗传学基础在很大程度上是未知的。我们在X区操纵了FoxP2亚型，X区是鸟类纹状体的一个类似于人类前纹状体的歌曲专一性区域，在歌曲发育的关键时期。我们第一次描述了每个亚型对声乐学习的独特贡献。对RNA-seq数据的加权基因共表达网络分析揭示了与歌唱、学习或声音变异性相关的基因模块。与歌唱相关的共表达在青少年和成人的X区被发现，而与学习相关的共表达仅在青少年中被发现。幼年斑马雀X区学习和歌唱共表达的融合可能强调了推动幼年斑马雀发声学习的分子过程，以此类推，人类也是如此。鸣禽和人类很像，在青年时期有一个关键时期，那是它们最擅长学习发声交流技能的时期。对于鸟类来说，这是他们学习一首歌的时候，他们将在以后的生活中将其用作求爱歌曲。对于人类来说，这是学习语言技能最容易的时候。在这一关键时期结束后，人们学习语言的难度就大了很多，某些鸟类也很难学习它们的歌声。当鸟儿每天早晨唱歌时，一种名为FoxP2的基因的活性会下降，这会导致数千个其他基因的活性发生协调变化。人们怀疑FoxP2及其引起的变化可能是声乐学习的分子基础的一部分。众所周知，Foxp2在人类的语言中也起到了作用，鸟类和人类都有这个基因的一个长版本和一个短版本。之前的研究表明，当该基因的长版本被改变，使其活动不再在鸟儿歌唱时减少时，鸟类无法学习它们的歌声。此外，携带Long版本突变的人类在语言方面也存在问题。然而，直到现在，人们还不知道对简短版本的修改是否具有同样的效果。Burkett等人。研究了在鸣禽的关键期前后，FoxP2的作用是否有明显的模式。分析发现，在关键时期，随着幼鸟学会唱歌，一组基因一起发生了变化。随着鸟类年龄的增长和关键期的结束，这种特殊的模式消失了。Burkett等人。证实了当鸟类的FoxP2的长版本发生改变时，它们的学习能力就会下降。然而，改变FoxP2的简短版本对学习几乎没有影响，反而导致了鸟儿歌唱的变化。已知在实验中发现的遗传途径存在于许多不同的物种中，包括人类。相关的途径也被发现在老鼠和蜗牛等远亲生物的非发声学习中发挥作用。这表明，它们可能是学习新技能的蓝图。到目前为止，由于对语音交流的分子基础缺乏了解，语言障碍的治疗方法还很少。这项研究的发现可能有助于为人类的言语问题创造新的治疗方法，例如患有自闭症的儿童或携带FoxP2突变版本的人。
Human speech is one of the few examples of vocal learning among mammals yet ~half of avian species exhibit this ability. Its neurogenetic basis is largely unknown beyond a shared requirement for FoxP2 in both humans and zebra finches. We manipulated FoxP2 isoforms in Area X, a song-specific region of the avian striatopallidum analogous to human anterior striatum, during a critical period for song development. We delineate, for the first time, unique contributions of each isoform to vocal learning. Weighted gene coexpression network analysis of RNA-seq data revealed gene modules correlated to singing, learning, or vocal variability. Coexpression related to singing was found in juvenile and adult Area X whereas coexpression correlated to learning was unique to juveniles. The confluence of learning and singing coexpression in juvenile Area X may underscore molecular processes that drive vocal learning in young zebra finches and, by analogy, humans. Songbirds, much like in humans, have a critical period in youth when they are best at learning vocal communication skills. In birds, this is when they learn a song they will use later in life as a courtship song. In humans, this is when language skills are most easily learned. After this critical period ends, it is much harder for people to learn languages, and for certain bird species to learn their song. When birds sing every morning, the activity of a gene called FoxP2 drops, which causes a coordinated change in the activity of thousands of other genes. It is suspected that FoxP2 – and the changes it causes – could be a part of the molecular basis for vocal learning. FoxP2 is also known to play a role in speech in humans, and both birds and humans have a long and a short version of this gene. Previous research has shown that when the long version of the gene was altered so its activity would no longer decrease when birds were singing, the birds failed to learn their song. Moreover, humans with a mutation in the long version have problems with their speech. However, until now, it was not known if modifications to the short version had the same effect. Burkett et al. investigated whether there was a noticeable pattern in the effects of FoxP2 before and after the critical period in a songbird. The analysis found that during the critical period, a set of genes changed together as young birds learned to sing. This particular pattern disappeared as the birds aged and the critical period ended. Burkett et al. confirmed that when birds had the long version of FoxP2 altered, they were less able to learn. However, changing the short version of FoxP2 had little effect on learning but led to changes in the birds’ song. The genetic pathways identified in the experiments are known to be present in many different species, including humans. Related pathways have also been found to play a role in non-vocal learning in organisms as distantly related as rats and snails. This suggests that they could be acting as a blueprint for learning new skills. Few treatments for language impairments have been developed so far due to poor understanding of the molecular basis for vocal communication. The findings of this study could help to create new treatments for speech problems in people, such as children with autism or people with mutated versions of FoxP2.
影响因子：
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作者：
Winograd, Claudia;Ceman, Stephanie
通讯作者：
Ceman, Stephanie