Myc suppresses male–male courtship in Drosophila

• Published in: The EMBO journal Vol. 41; no. 7; pp. e109905 - n/a
• Main Authors: Pan, Yu, Li, Wanzhen, Deng, Zhu, Sun, Yihao, Ma, Xianjue, Liang, Ruijuan, Guo, Xiaowei, Sun, Ying, Li, Wenzhe, Jiao, Renjie, Xue, Lei
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 04.04.2022; John Wiley and Sons Inc
• Subjects: Animals; Aromatic-L-amino-acid decarboxylase; Binding; Courtship; Ddc; Depletion; Dihydroxyphenylalanine; Dopamine; Dopamine - metabolism; Dopamine receptors; Dopaminergic Neurons - metabolism; Drosophila; Drosophila - physiology; Drosophila melanogaster - metabolism; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; Fruit flies; Gene deletion; Genetic factors; Genetic screening; Genome editing; Genomes; Insects; Male; Males; male–male courtship; Mutation; Myc; Myc protein; Natural selection; Nervous system; Neurons; Sexual behavior; Transcription; male-male courtship; Ddc; Dopamine; Drosophila; Myc
• ISSN: 0261-4189; 1460-2075
• DOI: 10.15252/embj.2021109905

Despite strong natural selection on species, same‐sex sexual attraction is widespread across animals, yet the underlying mechanisms remain elusive. Here, we report that the proto‐oncogene Myc is required in dopaminergic neurons to inhibit Drosophila male–male courtship. Loss of Myc, either by mutation or neuro‐specific knockdown, induced males’ courtship propensity toward other males. Our genetic screen identified DOPA decarboxylase (Ddc) as a downstream target of Myc. While loss of Ddc abrogated Myc depletion‐induced male–male courtship, Ddc overexpression sufficed to trigger such behavior. Furthermore, Myc‐depleted males exhibited elevated dopamine level in a Ddc‐dependent manner, and their male–male courtship was blocked by depleting the dopamine receptor DopR1. Moreover, Myc directly inhibits Ddc transcription by binding to a target site in the Ddc promoter, and deletion of this site by genome editing was sufficient to trigger male–male courtship. Finally, drug‐mediated Myc depletion in adult neurons by GeneSwitch technique sufficed to elicit male–male courtship. Thus, this study uncovered a novel function of Myc in preventing Drosophila male–male courtship, and supports the crucial roles of genetic factors in inter‐male sexual behavior. Synopsis Drosophila Myc is required in the nervous system to prevent male–male courtship in a DOPA decarboxylase (Ddc)‐dependent manner, and drug‐mediated Myc depletion in adult neurons suffices to elicit male–male courtship. Drosophila Myc is required in the nervous system to prevent male–male courtship. DOPA decarboxylase (Ddc) is necessary and sufficient for loss‐of‐Myc‐induced male–male courtship. Myc directly inhibits Ddc transcription by binding to a Myc target site (E‐box) in the Ddc promoter. Drug‐mediated Myc depletion in adult neurons suffices to elicit male–male courtship. The proto‐oncogene Myc is specifically required in dopaminergic neurons to repress DOPA decarboxylase transcription, reducing the levels of dopamine and suppressing male–male courtship in flies.