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Publication : Foxp2 controls synaptic wiring of corticostriatal circuits and vocal communication by opposing Mef2c.

First Author  Chen YC Year  2016
Journal  Nat Neurosci Volume  19
Issue  11 Pages  1513-1522
PubMed ID  27595386 Mgi Jnum  J:238211
Mgi Id  MGI:5818611 Doi  10.1038/nn.4380
Citation  Chen YC, et al. (2016) Foxp2 controls synaptic wiring of corticostriatal circuits and vocal communication by opposing Mef2c. Nat Neurosci 19(11):1513-1522
abstractText  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.
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