Drosophila Myc is Involved in Fly Circadian Behavior

Objective: We sought to determine whether Drosophila Myc will alter the molecular clock and circadian locomotor behavior in fruit fly. Background: Drosophila Myc (termed dMyc) is highly conserved with functional properties similar to the mammalian transcription factor Myc, including regulation of cell growth, development, and metabolism. We recently reported that mammalian Myc disrupts molecular clock by suppressing the major clock regulator Bmal1 and clock-regulated glucose metabolism in cultured cancer cells. However, the role of dMyc in Drosophila circadian biology is not known. Design/Methods: In this study, the locomotor activity and molecular clock expression of flies with gain-of-function of dMyc via UAS-Gal4 system and loss-of-function mutant of dMyc were individually tested and analyzed. Results: Here, we report that both gain-of-function and loss-of-function of dMyc can affect circadian locomotor behavior in flies. Using actigraphy to monitor circadian activity, we found that overexpression of dMyc in Pigment Dispersing Factor (PDF) and Cryptochrome (Cry) expressing cells result in higher percentage of arrhythmic flies. dMyc overexpression also induces several clock-controlled genes, such as cyc , tim , cry and cwo . Interestingly, flies with dMyc mutation exhibit severe arrhythmic phenotype, which can be rescued by additional mutation of dMnt, a known suppressor of dMyc activity. Loss of dMyc also alters the expression and oscillation of per and tim in the brain. Conclusions: Our results demonstrate a role of dMyc in modulating Drosophila circadian locomotor behavior potentially through directly regulating components of the core molecular clock as well as indirect effect on clock neuron development, clock outputs and metabolism. Disclosure: Dr. Hsieh has nothing to disclose. Dr. Zheng has nothing to disclose. Dr. Sehgal has nothing to disclose. Dr. Dang has nothing to disclose.