Human-specific transcriptional regulation of CNS development genes by FOXP2.
Human-specific transcriptional regulation of CNS development genes by FOXP2.
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作者：
人类大脑中协调语言进化和发展的信号通路仍然未知。到目前为止，转录因子FOXP2(叉头盒P2)是唯一与孟德尔式人类言语和语言障碍有关的基因。有人提出，FOXP2的人类变体的氨基酸组成经历了加速进化，这种变化发生在人类语言出现的时候。然而，这仍然存在争议，而且在人类FOXP2中获得这些氨基酸是否会对人类神经元产生任何功能影响仍未得到测试。在这里，我们证明了这两个氨基酸通过在体外进行差异转录调控来改变FOXP2的功能。我们在活体中将这些观察扩展到人类和黑猩猩的大脑，并使用网络分析来识别差异表达基因之间的新关系。这些数据为FOXP2在人类谱系上发生的变化的功能相关性提供了实验支持，突出了对人类大脑发育和疾病有直接影响的特定途径。由于FOXP2在人类的言语和语言中起着重要的作用，所识别的靶点可能在人类语言回路的发展和进化中具有关键功能。
The signaling pathways orchestrating both the evolution and development of language in the human brain remain unknown. To date, the transcription factor FOXP2 (forkhead box P2) is the only gene implicated in Mendelian forms of human speech and language dysfunction. It has been proposed, that the amino acid composition in the human variant of FOXP2 has undergone accelerated evolution, and this change occurred around the time of language emergence in humans. However, this remains controversial, and whether the acquisition of these amino acids in human FOXP2 has any functional consequence in human neurons remains untested. Here, we demonstrate that these two amino acids alter FOXP2 function by conferring differential transcriptional regulation in vitro. We extend these observations in vivo to human and chimpanzee brain, and use network analysis to identify novel relationships among the differentially expressed genes. These data provide experimental support for the functional relevance of changes in FOXP2 that occur on the human lineage, highlighting specific pathways with direct consequences for human brain development and disease. Since FOXP2 has an important role in speech and language in humans, the identified targets may have a critical function in the development and evolution of language circuitry in humans.
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影响因子：
9.8
作者：
Feuk, Lars;Kalervo, Aino;Hannula-Jouppi, Katariina
通讯作者：
Hannula-Jouppi, Katariina
DOI：
10.1073/pnas.0503739102
发表时间：
2005-07-05
影响因子：
11.1
作者：
Shu, WG;Cho, JY;Buxbaum, JD
通讯作者：
Buxbaum, JD
影响因子：
4.8
作者：
Konopka, Genevieve;Tekiela, Jackie;Duncan, Stephen A.
通讯作者：
Duncan, Stephen A.
影响因子：
9.8
作者：
Uhlenberg, B;Schuelke, M;Gärtner, J
通讯作者：
Gärtner, J
影响因子：
14.8
作者：
Khattak, Shahryar;Murawala, Prayag;Tanaka, Elly M.
通讯作者：
Tanaka, Elly M.