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 Area X,
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
