Foxp2 controls synaptic wiring of corticostriatal circuits and vocal communication by opposing Mef2c
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 c...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
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Springer Nature
2017
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| Online Access: | http://hdl.handle.net/1721.1/112187 https://orcid.org/0000-0002-4326-7720 |
| _version_ | 1826201139983417344 |
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| author | 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 Pääbo, Svante Graybiel, Ann M Liu, Fu-Chin |
| author2 | McGovern Institute for Brain Research at MIT |
| author_facet | McGovern Institute for Brain Research at MIT 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 Pääbo, Svante Graybiel, Ann M Liu, Fu-Chin |
| author_sort | Chen, Yi-Chuan |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T11:46:50Z |
| format | Article |
| id | mit-1721.1/112187 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T11:46:50Z |
| publishDate | 2017 |
| publisher | Springer Nature |
| record_format | dspace |
| spelling | mit-1721.1/1121872022-10-01T05:59:52Z Foxp2 controls synaptic wiring of corticostriatal circuits and vocal communication by opposing Mef2c 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 Pääbo, Svante Graybiel, Ann M Liu, Fu-Chin McGovern Institute for Brain Research at MIT Graybiel, Ann M 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. National Institutes of Health (U.S.) (Grant R37 HD028341) Eunice Kennedy Shriver National Institute of Child Health and Human Development (U.S.) (Award R37 HD028341) 2017-11-14T18:59:15Z 2017-11-14T18:59:15Z 2016-09 2016-05 2017-11-09T16:47:21Z Article http://purl.org/eprint/type/JournalArticle 1097-6256 1546-1726 http://hdl.handle.net/1721.1/112187 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 https://orcid.org/0000-0002-4326-7720 http://dx.doi.org/10.1038/NN.4380 Nature Neuroscience 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. application/pdf Springer Nature PMC |
| spellingShingle | 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 Pääbo, Svante Graybiel, Ann M Liu, Fu-Chin Foxp2 controls synaptic wiring of corticostriatal circuits and vocal communication by opposing Mef2c |
| title | Foxp2 controls synaptic wiring of corticostriatal circuits and vocal communication by opposing Mef2c |
| title_full | Foxp2 controls synaptic wiring of corticostriatal circuits and vocal communication by opposing Mef2c |
| title_fullStr | Foxp2 controls synaptic wiring of corticostriatal circuits and vocal communication by opposing Mef2c |
| title_full_unstemmed | Foxp2 controls synaptic wiring of corticostriatal circuits and vocal communication by opposing Mef2c |
| title_short | Foxp2 controls synaptic wiring of corticostriatal circuits and vocal communication by opposing Mef2c |
| title_sort | foxp2 controls synaptic wiring of corticostriatal circuits and vocal communication by opposing mef2c |
| url | http://hdl.handle.net/1721.1/112187 https://orcid.org/0000-0002-4326-7720 |
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