FoxP1 orchestration of ASD-relevant signaling pathways in the striatum

Daniel J. Araujo, Ashley G. Anderson, Stefano Berto, Wesley Runnels, Matthew Harper, Simon Ammanuel, Michael A. Rieger, Hung Chung Huang, Kacey Rajkovich, Kristofer W. Loerwald, Joseph D. Dekker, Haley O. Tucker, Joseph D. Dougherty, Jay R. Gibson, Genevieve Konopka

Research output: Contribution to journalArticlepeer-review

70 Scopus citations


Mutations in the transcription factor Forkhead box p1 (FOXP1) are causative for neurodevelopmental disorders such as autism. However, the function of FOXP1 within the brain remains largely uncharacterized. Here, we identify the gene expression program regulated by FoxP1 in both human neural cells and patient-relevant heterozygous Foxp1 mouse brains. We demonstrate a role for FoxP1 in the transcriptional regulation of autism-related pathways as well as genes involved in neuronal activity. We show that Foxp1 regulates the excitability of striatal medium spiny neurons and that reduction of Foxp1 correlates with defects in ultrasonic vocalizations. Finally, we demonstrate that FoxP1 has an evolutionarily conserved role in regulating pathways involved in striatal neuron identity through gene expression studies in human neural progenitors with altered FOXP1 levels. These data support an integral role for FoxP1 in regulating signaling pathways vulnerable in autism and the specific regulation of striatal pathways important for vocal communication.

Original languageEnglish
Pages (from-to)2081-2096
Number of pages16
JournalGenes and Development
Issue number20
StatePublished - Oct 15 2015


  • Autism
  • Gene expression
  • Neuronal activity
  • Striatum
  • Ultrasonic vocalizations


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