Myc suppresses male–male courtship in Drosophila
Myc suppresses male–male courtship in Drosophila
复制标题
DOI：
10.15252/embj.2021109905
复制
发表时间：
2022-02
期刊：
影响因子：
--
通讯作者：
Yu Pan;Wanzhen Li;Zhu Deng;Yihao Sun;Xianjue Ma;Ruijuan Liang;Xiaowei Guo;Ying Sun;Wenzhe Li;R. Jiao;L. Xue
中科院分区：
文献类型：
--
作者：
Yu Pan;Wanzhen Li;Zhu Deng;Yihao Sun;Xianjue Ma;Ruijuan Liang;Xiaowei Guo;Ying Sun;Wenzhe Li;R. Jiao;L. Xue
尽管物种存在强烈的自然选择，同性性吸引在动物中普遍存在，但其潜在机制仍然难以捉摸。在此，我们报道多巴胺能神经元需要原癌基因 Myc 来抑制果蝇雄性之间的求爱。通过突变或神经特异性敲低而导致的 Myc 缺失，会诱导雄性对其他雄性的求爱倾向。我们的基因筛选发现多巴脱羧酶 (Ddc) 是 Myc 的下游靶标。虽然 Ddc 的缺失消除了 Myc 耗竭引起的雄性求爱，但 Ddc 的过度表达足以引发这种行为。此外，Myc 缺失的雄性以 Ddc 依赖性方式表现出多巴胺水平升高，并且它们的雄性求爱通过耗尽多巴胺受体 DopR1 而被阻断。此外，Myc 通过与 Ddc 启动子中的目标位点结合直接抑制 Ddc 转录，通过基因组编辑删除该位点足以触发雄性与雄性求爱。最后，通过 GeneSwitch 技术在成年神经元中药物介导的 Myc 耗竭足以引发雄性之间的求爱。因此，这项研究发现了 Myc 在阻止果蝇雄性求爱方面的新功能，并支持遗传因素在雄性间性行为中的关键作用。
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.