Myc Regulates Male-male Courtship Behavior In Drosophila

Faced with strong natural selection,the ability of an organism to distinguish the sex of others and to choose potential mating partners of the opposite sex is crucial for propagation of the species.Although it appears to have a considerable time and energy cost without any apparent reproductive benefits,homosexual behavior does retain in the population across animal evolution process.Today,homosexuality has been observed in about 1000 species.As homosexuality-related research involves ethical and moral issues,as well as the complexity of sexual orientation research itself,the current research has not yet reached a unified conclusion that can explain the phenomenon of homosexuality.Myc is a well-studied proto-oncogene that plays pivotal roles in development and tumor progression.When we investigated the role of Myc in tumor invasion and cell migration,we accidently noticed an increased occurrence of male-male interaction among Myc^dm-1 mutant males.We found that Myc is required to prevent male-male courtship,and loss of Myc does not alter male’s sexual preference.Courtship is an instinctive behavior regulated by neural circuits.Knockdown Myc in the nervous system resulted in increased male-male courtship.By contrast,knockdown Myc in muscle or fat body did not elicit male-male courtship.Next,we performed a large scale genetic screen for dominant modifiers of Myc depletion-induced male-male courtship behavior.Within the overlapping region,we identified dopa decarboxylase（Ddc）as a strong candidate.Consistently,Myc depletion-induced male-male courtship was blocked by depleting Ddc,and knockdown of the dopamine receptor gene Dop R1 also suppressed Myc depletion-induced male-male courtship.In addition,we found that overexpression of Ddc triggered male-male courtship.Ddc is a central enzyme leading to the synthesis of dopamine.We found that dopamine concentration was elevated in loss of Myc males,which was suppressed in deplting Ddc.As a transcriptional factor,Myc can activating or repressing target gene expression by binding to E-box.We found Ddc transcription was increased in Myc-depleted males.According to bioinformatics analysis,we identified two putative Myc binding motifs in the promoter and intron respectively.As a result,we found that Myc inhibits Ddc transcription through binding to E-box located in the promoter,consistent with the conclusion in chromatin immunoprecipitation（Ch IP）.Finally,we found deletion of E1 from the genome is sufficient to elevate Ddc-mediated dopamine synthesis and elicit male-male courtship in males.Forthermore,drug-mediated（RU486）depletion of Myc in adult neurons significantly enhanced males’courtship tendency towards other males.In summary,these fingdings not only extended our knowledge of Myc function in male-male courtship,shed a light on the molecular mechanism of Myc depletion-induced male-male courtship,but also provided novel genetic evidence of male-male courtship in Drosophila.