Foxp2 controls synaptic wiring of corticostriatal circuits and vocal communication by opposing Mef2c
2016
Details
- Autor(en) / Beteiligte
- Titel
- Foxp2 controls synaptic wiring of corticostriatal circuits and vocal communication by opposing Mef2c
- Ist Teil von
- Nature neuroscience, 2016-11, Vol.19 (11), p.1513
- Ort / Verlag
- United States
- Erscheinungsjahr
- 2016
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- eISSN: 1546-1726DOI: 10.1038/nn.4380Titel-ID: cdi_pubmed_primary_27595386
- Format
- –
- Schlagworte
- Animals, Autism Spectrum Disorder - genetics, Basal Ganglia - metabolism, Communication, Corpus Striatum - metabolism, Forkhead Transcription Factors - metabolism, Learning - physiology, MEF2 Transcription Factors - genetics, Mice, Transgenic, Neural Pathways - metabolism, Repressor Proteins - metabolism, Vocalization, Animal - physiology