Drosophila FoxP Mutants Are Deficient in Operant Self-Learning

PLoS One. 2014 Jun 25;9(6):e100648. doi: 10.1371/journal.pone.0100648. eCollection 2014.


Intact function of the Forkhead Box P2 (FOXP2) gene is necessary for normal development of speech and language. This important role has recently been extended, first to other forms of vocal learning in animals and then also to other forms of motor learning. The homology in structure and in function among the FoxP gene members raises the possibility that the ancestral FoxP gene may have evolved as a crucial component of the neural circuitry mediating motor learning. Here we report that genetic manipulations of the single Drosophila orthologue, dFoxP, disrupt operant self-learning, a form of motor learning sharing several conceptually analogous features with language acquisition. Structural alterations of the dFoxP locus uncovered the role of dFoxP in operant self-learning and habit formation, as well as the dispensability of dFoxP for operant world-learning, in which no motor learning occurs. These manipulations also led to subtle alterations in the brain anatomy, including a reduced volume of the optic glomeruli. RNAi-mediated interference with dFoxP expression levels copied the behavioral phenotype of the mutant flies, even in the absence of mRNA degradation. Our results provide evidence that motor learning and language acquisition share a common ancestral trait still present in extant invertebrates, manifest in operant self-learning. This 'deep' homology probably traces back to before the split between vertebrate and invertebrate animals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / metabolism
  • Brain / physiology
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / genetics*
  • Drosophila melanogaster / physiology*
  • Female
  • Flight, Animal
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism*
  • Habits
  • Learning*
  • Mutagenesis, Insertional
  • Mutant Proteins / genetics
  • Mutant Proteins / metabolism*
  • Mutation*
  • Vocalization, Animal / physiology


  • Drosophila Proteins
  • Forkhead Transcription Factors
  • FoxP protein, Drosophila
  • Mutant Proteins

Associated data

  • figshare/10.6084/M9.FIGSHARE.740444

Grant support

This study was funded by the research commission of the FU Berlin (to HJP and CS) and the DFG (BR 1892/6-1 and BR 1892/7-1 to BB). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.