Foxp2 controls synaptic wiring of corticostriatal circuits and vocal communication by opposing Mef2c
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Author(s)
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
Date Issued
September 2016
Journal
Nature Neuroscience
Publisher
Springer Nature
Citation
Chen, Yi-Chuan et al. “Foxp2 Controls Synaptic Wiring of Corticostriatal Circuits and Vocal Communication by Opposing Mef2c.” Nature Neuroscience 19, 11 (September 2016): 1513–1522. © Nature America, Inc., part of Springer Nature
Version
Author's final manuscript
Abstract
Cortico-basal ganglia circuits are critical for speech and language and are implicated in autism spectrum disorder, in which language function can be severely affected. We demonstrate that in the mouse striatum, the gene Foxp2 negatively interacts with the synapse suppressor gene 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.
MIT Department
McGovern Institute for Brain Research at MIT
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1038/NN.4380
