Adam I, Mendoza E, Kobalz U, Wohlgemuth S, Scharff C
Department for Animal Behavior, Freie Universität Berlin, Berlin, Germany.
Genes Brain Behav. 2017 Jul;16(6):635-642. doi: 10.1111/gbb.12390. Epub 2017 Jun 22.
Mutations of FOXP2 are associated with altered brain structure, including the striatal part of the basal ganglia, and cause a severe speech and language disorder. Songbirds serve as a tractable neurobiological model for speech and language research. Experimental downregulation of FoxP2 in zebra finch Area X, a nucleus of the striatal song control circuitry, affects synaptic transmission and spine densities. It also renders song learning and production inaccurate and imprecise, similar to the speech impairment of patients carrying FOXP2 mutations. Here we show that experimental downregulation of FoxP2 in Area X using lentiviral vectors leads to reduced expression of CNTNAP2, a FOXP2 target gene in humans. In addition, natural downregulation of FoxP2 by age or by singing also downregulated CNTNAP2 expression. Furthermore, we report that FoxP2 binds to and activates the avian CNTNAP2 promoter in vitro. Taken together these data establish CNTNAP2 as a direct FoxP2 target gene in songbirds, likely affecting synaptic function relevant for song learning and song maintenance.
FOXP2基因的突变与大脑结构改变有关，包括基底神经节的纹状体部分，并会导致严重的言语和语言障碍。鸣禽是用于言语和语言研究的易于处理的神经生物学模型。在斑胸草雀的X区（纹状体鸣唱控制回路的一个核团）中，通过实验下调FoxP2会影响突触传递和树突棘密度。这也会使鸣唱学习和发声变得不准确、不精确，类似于携带FOXP2突变的患者的言语障碍。在这里，我们表明，使用慢病毒载体在X区实验性下调FoxP2会导致CNTNAP2（人类中的一个FOXP2靶基因）的表达降低。此外，随着年龄增长或通过鸣唱自然下调FoxP2也会下调CNTNAP2的表达。此外，我们报告称，FoxP2在体外与鸟类CNTNAP2启动子结合并激活该启动子。综合这些数据表明，CNTNAP2是鸣禽中直接的FoxP2靶基因，可能影响与鸣唱学习和鸣唱维持相关的突触功能。
