Conserved Role Of Drosophila Melanogaster Foxp In Motor Coordination And Courtship Song

Abstract

FoxP2 is a transcription factor underlying a severe human speech and language disorder. Research on this gene in vertebrate model organisms such as mouse and zebra finch indicated that it is highly conserved between species and strongly expressed in motor related brain structures. Although these studies implicated FoxP2 in development of motor control regions, the precise mechanisms are not understood. This work is the first to explore the functional role of FoxP2's Drosophila homolog known as FoxP. We characterize the behavioral importance of this gene in flies using FoxP specific RNA interference throughout development, which impairs several types of behavior, with males more strongly affected. We also used a temperature sensitive UAS-Shibire line to disrupt FoxP neuron function in adulthood and we saw dramatic effects on motor coordination. Our work also provides the first visualization of FoxP expression in the fly brain. We see a small number of symmetrically expressed FoxP neurons in clusters throughout the brain, but no obvious difference between males and females. There is also strong FoxP expression in the protocerebral bridge within the central complex, which is essential for higher level locomotion control and is thought to be homologous to the vertebrate basal ganglia. FoxP2 in humans is also highly expressed in the basal ganglia, specifically in areas important for motor coordination. These results indicate a conserved functional homology of this gene between invertebrates and vertebrates, both in terms of behavioral effects on motor coordination as well as expression pattern. We also disrupted FoxP neurons throughout pupal stages and discover that eclosion behavior is abolished, indicating a possible role of FoxP in development during pupation. Thus we propose to establish Drosophila as a model to study this crucial speech disease gene. We believe this work will contribute to further understanding of the importance of FoxP transcription factors in humans, as well as provide further support for the idea of deep homology between the invertebrate and vertebrate brain.