Drosophila and experimental neurology in the post-genomic era

Exp Neurol. 2015 Dec;274(Pt A):4-13. doi: 10.1016/j.expneurol.2015.03.016. Epub 2015 Mar 24.


For decades, the fruit fly, Drosophila melanogaster, has been among the premiere genetic model systems for probing fundamental neurobiology, including elucidation of mechanisms responsible for human neurologic disorders. Flies continue to offer virtually unparalleled versatility and speed for genetic manipulation, strong genomic conservation, and a nervous system that recapitulates a range of cellular and network properties relevant to human disease. I focus here on four critical challenges emerging from recent advances in our understanding of the genomic basis of human neurologic disorders where innovative experimental strategies are urgently needed: (1) pinpointing causal genes from associated genomic loci; (2) confirming the functional impact of allelic variants; (3) elucidating nervous system roles for novel or poorly studied genes; and (4) probing network interactions within implicated regulatory pathways. Drosophila genetic approaches are ideally suited to address each of these potential translational roadblocks, and will therefore contribute to mechanistic insights and potential breakthrough therapies for complex genetic disorders in the coming years. Strategic collaboration between neurologists, human geneticists, and the Drosophila research community holds great promise to accelerate progress in the post-genomic era.

Keywords: Animal model; Complex genetics; Drosophila melanogaster; Epistasis; Exome sequencing; Genome-wide association study; Genomics; Mendelian disease; Neurology.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Drosophila
  • Drosophila Proteins / genetics*
  • Gene Regulatory Networks / genetics
  • Genetic Predisposition to Disease / genetics
  • Genomics / methods
  • Genomics / trends*
  • Humans
  • Nervous System Diseases / genetics*
  • Nervous System Diseases / pathology
  • Neurology / methods
  • Neurology / trends*


  • Drosophila Proteins