CNTNAP2 is a direct FoxP2 target in vitro and in vivo in zebra finches: Complex regulation by age and activity

I. Adam*, E. Mendoza, U. Kobalz, Sandra Wohlgemuth, C. Scharff

*Corresponding author for this work

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Mutations of FOXP2 are associated with altered brain structure, including the striatal part of the basal ganglia, and cause a severe speech and language disorder. Songbirds serve as a tractable neurobiological model for speech and language research. Experimental downregulation of FoxP2 in zebra finch AreaX, a nucleus of the striatal song control circuitry, affects synaptic transmission and spine densities. It also renders song learning and production inaccurate and imprecise, similar to the speech impairment of patients carrying FOXP2 mutations. Here we show that experimental downregulation of FoxP2 in Area X using lentiviral vectors leads to reduced expression of CNTNAP2, a FOXP2 target gene in humans. In addition, natural downregulation of FoxP2 by age or by singing also downregulated CNTNAP2 expression. Furthermore, we report that FoxP2 binds to and activates the avian CNTNAP2 promoter in vitro. Taken together these data establish CNTNAP2 as a direct FoxP2 target gene in songbirds, likely affecting synaptic function relevant for song learning and song maintenance.

Original languageEnglish
JournalGenes, Brain and Behavior
Issue number6
Pages (from-to)635–642
Publication statusPublished - 2017


  • EMSA
  • FoxP2
  • Gene expression
  • Luciferase assay
  • QPCR
  • Songbird
  • Spiny neurons
  • Striatum
  • Vocal learning
  • Zebra finch


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