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Here, we characterized cortex-specific Foxp2 conditional knockout mice and found a major deficit in reversal learning, a form of behavioral flexibility. In contrast, they showed normal activity levels, anxiety, and vocalizations, save for a slight decrease in neonatal call loudness. These behavioral phenotypes were accompanied by decreased cortical dopamine D1 receptor (D1R) expression at neonatal and adult stages, while general cortical development remained unaffected. Finally, using single-cell transcriptomics, we identified at least five excitatory and three inhibitory D1R-expressing cell types in neonatal frontal cortex, and we found changes in D1R cell type composition and gene expression upon cortical Foxp2 deletion. Strikingly, these alterations included non-cell-autonomous changes in upper layer neurons and interneurons. Together, these data support a role for Foxp2 in the development of dopamine-modulated cortical circuits and behaviors relevant to NDDs.<\/jats:p>","DOI":"10.1093\/cercor\/bhz209","type":"journal-article","created":{"date-parts":[[2019,8,19]],"date-time":"2019-08-19T15:23:42Z","timestamp":1566228222000},"page":"1855-1870","source":"Crossref","is-referenced-by-count":48,"title":["Cortical Foxp2 Supports Behavioral Flexibility and Developmental Dopamine D1 Receptor Expression"],"prefix":"10.1093","volume":"30","author":[{"given":"Marissa","family":"Co","sequence":"first","affiliation":[{"name":"Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie L","family":"Hickey","sequence":"first","affiliation":[{"name":"Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashwinikumar","family":"Kulkarni","sequence":"first","affiliation":[{"name":"Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Harper","sequence":"first","affiliation":[{"name":"Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3363-7302","authenticated-orcid":false,"given":"Genevieve","family":"Konopka","sequence":"first","affiliation":[{"name":"Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX, 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