Modeling human cognitive impairment candidate genes in Drosophila Melanogaster: report on a systematic study on locomotor behavior

Background and Aim : Understanding function of the brain and molecular pathways underlying complex behavior of cognitive function is a major challenge. With the advent of next-generation sequencing techniques, the number of candidate genes for cognitive disorders has increased dramatically; but the role of their related proteins in neuronal network remains largely unknown. In the context of a systematic study to investigate novel intellectual disability (ID) candidate genes, a series of functional and behavioral experiments in a well-known model organism, Drosophila Melanogaster, has been done. Many basic biological, physiological, and neurological properties are conserved between humans and Drosophila Melanogaster, and nearly 75% of human disease-causing genes are believed to have a functional homolog in this tiny organism.Methods : Locomotion, is a complex behavior, which is required for localization of food and mates, and response to stress, and is, therefore, an integral component of most animal behaviors. Basic biological processes, including development of nervous system, are evolutionarily conserved between flies and mammals. Thus, orthologues of the genes affecting Drosophila locomotion may well be relevant in humans. To screen the effect of knock down of ID candidate genes by a UAS-GAL4 system, quantitative climbing assay has been done in Drosophila Melanogaster.Results : We found that flies have a progressive locomotor defect following knocking down of orthologous of RHBDF1 (rhomboid 5 homolog 1), and Cytochrome C Oxidase Subunit 6C (COX6C). We also observed that knockdown of COX6C decreased life span and increased fly mortality.Conclusion : These results confirmed the role of RHBDF1 and COX6C genes in animal behavior and cognition. Further investigations into the role of several other novel ID candidate genes are ongoing.

کلیدواژه ها:

Drosophila melanogaster ، functional study ، locomotion assay