Conserved role of Drosophila melanogaster FoxP in motor coordination and courtship song.

FoxP2 is a highly conserved vertebrate transcription factor known for its importance in human speech and language production. Disruption of FoxP2 in several vertebrate models indicates a conserved functional role for this gene in both sound production and motor coordination. Although FoxP2 is known to be strongly expressed in brain regions important for motor coordination, little is known about FoxP2's role in the nervous system. The recent discovery of the well-conserved Drosophila melanogaster homolog, FoxP, provides an opportunity to study the role of this crucial gene in an invertebrate model. We hypothesized that, like FoxP2, Drosophila FoxP is important for behaviors requiring fine motor coordination. We used targeted RNA interference to reduce expression of FoxP and assayed the effects on a variety of adult behaviors. Male flies with reduced FoxP expression exhibit decreased levels of courtship behavior, altered pulse-song structure, and sex-specific motor impairments in walking and flight. Acute disruption of synaptic activity in FoxP expressing neurons using a temperature-sensitive shibire allele dramatically impaired motor coordination. Utilizing a GFP reporter to visualize FoxP in the fly brain reveals expression in relatively few neurons in distributed clusters within the larval and adult CNS, including distinct labeling of the adult protocerebral bridge - a section of the insect central complex known to be important for motor coordination and thought to be homologous to areas of the vertebrate basal ganglia. Our results establish the necessity of this gene in motor coordination in an invertebrate model and suggest a functional homology with vertebrate FoxP2.