A high throughput and sensitive method correlates neuronal disorder genotypes to Drosophila larvae crawling phenotypes

Fly (Austin). 2012 Oct-Dec;6(4):303-8. doi: 10.4161/fly.21582. Epub 2012 Sep 19.

Abstract

Drosophila melanogaster is widely used as a model system for development and disease. Due to the homology between Drosophila and human genes, as well as the tractable genetics of the fly, its use as a model for neurologic disorders, in particular, has been rising. Locomotive impairment is a commonly used diagnostic for screening and characterization of these models, yet a fast, sensitive and model-free method to compare behavior is lacking. Here, we present a high throughput method to quantify the crawling behavior of larvae. We use the mean squared displacement as well as the direction autocorrelation of the crawling larvae as descriptors of their motion. By tracking larvae from wild-type strains and models of the Fragile X mental retardation as well as Alzheimer disease, we show these mutants exhibit impaired crawling. We further show that the magnitude of impairment correlates with the severity of the mutation, demonstrating the sensitivity and the dynamic range of the method. Finally, we study larvae with altered expression of the shaggy gene, a homolog of Glycogen Synthase Kinase-3 (GSK-3), which has been implicated in Alzheimer disease. Surprisingly, we find that both increased and decreased expression of dGSK-3 lead to similar larval crawling impairment. These findings have implications for the use of GSK-3 inhibitors recently proposed for Alzheimer treatment.

Publication types

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

MeSH terms

  • Animals
  • Drosophila / genetics*
  • Drosophila / physiology
  • Drosophila Proteins / genetics
  • Fragile X Mental Retardation Protein / genetics
  • Genetic Association Studies
  • Genotype*
  • Glycogen Synthase Kinase 3 / genetics
  • Image Processing, Computer-Assisted
  • Larva / genetics
  • Larva / physiology
  • Locomotion / genetics*
  • Mutation
  • Phenotype
  • Time-Lapse Imaging

Substances

  • Drosophila Proteins
  • FMR1 protein, Drosophila
  • Fragile X Mental Retardation Protein
  • Sgg protein, Drosophila
  • Glycogen Synthase Kinase 3