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

Brandon R. Jakubowski, Rafael A. Longoria, George Shubeita

    Research output: Contribution to journalArticle

    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.

    Original languageEnglish (US)
    JournalFly
    Volume6
    Issue number4
    DOIs
    StatePublished - Jan 1 2012

    Fingerprint

    Drosophila
    phenotype
    genotype
    larvae
    Alzheimer disease
    methodology
    nervous system diseases
    autocorrelation
    Drosophila melanogaster
    genes
    screening
    mutation
    mutants
    tau-protein kinase

    Keywords

    • Alzheimer's disease
    • Behavior
    • Crawling
    • Disease model
    • FMR1
    • Fragile X syndrome
    • GSK-3
    • Larva
    • Neurodegeneration
    • Shaggy

    ASJC Scopus subject areas

    • Insect Science

    Cite this

    A high throughput and sensitive method correlates neuronal disorder genotypes to drosophila larvae crawling phenotypes. / Jakubowski, Brandon R.; Longoria, Rafael A.; Shubeita, George.

    In: Fly, Vol. 6, No. 4, 01.01.2012.

    Research output: Contribution to journalArticle

    Jakubowski, Brandon R. ; Longoria, Rafael A. ; Shubeita, George. / A high throughput and sensitive method correlates neuronal disorder genotypes to drosophila larvae crawling phenotypes. In: Fly. 2012 ; Vol. 6, No. 4.
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