Foxp2 controls synaptic wiring of corticostriatal circuits and vocal communication by opposing Mef2c.
Foxp2 controls synaptic wiring of corticostriatal circuits and vocal communication by opposing Mef2c.
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DOI：
10.1038/nn.4380
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发表时间：
2016-11
影响因子：
25
通讯作者：
Liu, Fu-Chin
中科院分区：
文献类型：
--
作者：
Chen, Yi-Chuan;Kuo, Hsiao-Ying;Bornschein, Ulrich;Takahashi, Hiroshi;Chen, Shih-Yun;Lu, Kuan-Ming;Yang, Hao-Yu;Chen, Gui-May;Lin, Jing-Ruei;Lee, Yi-Hsin;Chou, Yun-Chia;Cheng, Sin-Jhong;Chien, Cheng-Ting;Enard, Wolfgang;Hevers, Wulf;Paeaebo, Svante;Graybiel, Ann M.;Liu, Fu-Chin
皮质-基底神经节回路对言语和语言至关重要，并与自闭症谱系障碍（ASD）有关，其中语言功能可能受到严重影响。我们证明，在纹状体，基因，Foxp 2，负相互作用的突触抑制，Mef 2C。我们目前的因果关系的证据表明，Mef 2C抑制Foxp 2在新生小鼠纹状体控制皮质纹状体的输入和新生儿发声的突触发生。Mef 2C抑制皮质纹状体突触形成和纹状体棘发生，但本身可以通过直接DNA结合被Foxp 2抑制。Foxp 2缺失去抑制Mef 2C，并且Mef 2C的纹状体内和全局减少都拯救Foxp 2缺失突变体的发声和纹状体棘发生缺陷。这些发现表明，Foxp 2-Mef 2C信号是关键的皮质纹状体回路的形成。如果在人类中发现，这种信号缺陷可能会导致一系列神经和神经精神疾病。
Cortico-basal ganglia circuits are critical for speech and language and are implicated in autism spectrum disorder (ASD), in which language function can be severely affected. We demonstrate that in the striatum, the gene, Foxp2, negatively interacts with the synapse suppressor, Mef2C. We present causal evidence that Mef2C inhibition by Foxp2 in neonatal mouse striatum controls synaptogenesis of corticostriatal inputs and vocalization in neonates. Mef2C suppresses corticostriatal synapse formation and striatal spinogenesis, but can, itself, be repressed by Foxp2 through direct DNA binding. Foxp2 deletion de-represses Mef2C, and both intrastriatal and global decrease of Mef2C rescue vocalization and striatal spinogenesis defects of Foxp2-deletion mutants. These findings suggest that Foxp2-Mef2C signaling is critical to corticostriatal circuit formation. If found in humans, such signaling defects could contribute to a range of neurologic and neuropsychiatric disorders.
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影响因子：
2.9
作者：
Crittenden JR;Graybiel AM
通讯作者：
Graybiel AM
影响因子：
56.9
作者：
Morrow, Eric M.;Yoo, Seung-Yun;Flavell, Steven W.;Kim, Tae-Kyung;Lin, Yingxi;Hill, Robert Sean;Mukaddes, Nahit M.;Balkhy, Soher;Gascon, Generoso;Hashmi, Asif;Al-Saad, Samira;Ware, Janice;Joseph, Robert M.;Greenblatt, Rachel;Gleason, Danielle;Ertelt, Julia A.;Apse, Kira A.;Bodell, Adria;Partlow, Jennifer N.;Barry, Brenda;Yao, Hui;Markianos, Kyriacos;Ferland, Russell J.;Greenberg, Michael E.;Walsh, Christopher A.
通讯作者：
Walsh, Christopher A.
影响因子：
9.2
作者：
Groszer, Matthias;Keays, David A.;Deacon, Robert M. J.;de Bono, Joseph P.;Prasad-Mulcare, Shweta;Gaub, Simone;Baum, Muriel G.;French, Catherine A.;Nicod, Jrme;Coventry, Julie A.;Enard, Wolfgang;Fray, Martin;Brown, Steve D. M.;Nolan, Patrick M.;Paeaebo, Svante;Channon, Keith M.;Costa, Rui M.;Eilers, Jens;Ehret, Guenter;Nicholas, J.;Rawlins, P.;Fisher, Simon E.
通讯作者：
Fisher, Simon E.
DOI：
10.1523/jneurosci.0181-11.2011
发表时间：
2011-08-10
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Mukamel Z;Konopka G;Wexler E;Osborn GE;Dong H;Bergman MY;Levitt P;Geschwind DH
通讯作者：
Geschwind DH
影响因子：
10.6
作者：
Di Martino, Adriana;Kelly, Clare;Grzadzinski, Rebecca;Zuo, Xi-Nian;Mennes, Maarten;Angeles Mairena, Maria;Lord, Catherine;Castellanos, F. Xavier;Milham, Michael P.
通讯作者：
Milham, Michael P.