Ecdysone modulation of sexual behavior in Drosophila melanogaster

蜕皮激素对黑腹果蝇性行为的调节

• 批准号: 7456750
• 负责人: GEOFFREY GANTER
• 金额: $ 20.78万
• 依托单位: UNIVERSITY OF NEW ENGLAND
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7456750
• 关键词: Abdomen; Adult; Alleles; Animal Model; Animals; Attention; Behavior; Behavior Control; Biological Assay; Biological Models; Bisexual; Brain; Brain region; Copulation; Courtship; Data; Development; Developmental Biology; Drosophila genus; Drosophila melanogaster; Drug abuse; Ecdysone; Ecdysterone; Embryonic Development; Enhancers; Event; Female; Gender; Genes; Genetic; Hormonal; Hormones; Human; Lateral; Lead; Life; Liquid substance; Modeling; Motivation; Nature; Nervous system structure; Organism; Partner in relationship; Phenotype; Plastics; Preenings; Production; Public Health; Receptor Gene; Regulation; Research; Role; Series; Sex Behavior; Signal Transduction; Sleep; Steroids; Study models; System; Temperature; Testing; Time; Women' s Role; addiction; base; brain behavior; court; day; deprivation; design; ecdysone receptor; fly; interest; knowledge base; male; memory process; neurogenetics; preference; receptor function; reproductive function; research study; steroid hormone

DESCRIPTION (provided by applicant): We will explore the control of sexual behavior of the fruit fly by the steroid hormone ecdysone. The Drosophila melanogaster model system has produced a quantity of data relevant to higher functions of the human nervous system, including findings in memory processing, sleep, drug abuse and addiction. Exploration of the neurogenetic and hormonal mechanisms controlling sexual behavior in flies will increase our understanding of this important part of human life. Regulation of fruit fly courtship by ecdysone, the fly's only known steroid hormone is previously unknown, despite the wealth of information on courtship behavior. Using a temperature sensitive allele (nonfunctional at 290C) of the ecdysone receptor (EcR) gene we have shown that when EcR activity is impaired in adult males, elevated male-male courtship results (Ganter et al. 2007). We have confirmed the relationship between ecdysone signaling and sexual behavior using the ecd1 temperature-sensitive allele of the ecdysone availability gene ecdysoneless. These results suggest that ecdysone signaling in the adult male is necessary for modulation of sexual motivation, and that sexual behavior is plastic in the adult male fly, neither finding having been shown before. These results establish the fruit fly as a valid model for the study of hormonal control of behavior, with implications extending to higher organisms such as humans. We will now characterize the nature of ecdysone's role in sexual behavior. Specific Aim 1: Characterize the effects of EcR deficiency in brain regions known to be involved in sexual behavior. We will an enhancer trap Gal4 strategy reducing EcR function in courtship initiation regions in the brain, and then assaying for changes in sexual behavior. Specific Aim 2: Characterize the effects of ecdysone signaling hypomorphy on female sexual motivation. Our recent preliminary results suggest that modulation of female sexual motivation may be dependent on ecdysone signaling. We will confirm this result and further test the hypothesis that ecdysone signaling is required for modulation of sexual motivation in adult female flies with a series of experiments focused on female precopulatory behavior. Specific Aim 3: Characterize the developmental profile of ecdysone sensitivity of the adult brain. We will characterize the developmental biology of ecdysone sensitivity by manipulating the ecdysone system at various timepoints and for varying durations. We have implicated this steroid hormone in the modulation of sexual behavior in this tractable model organism, and the results will help us understand how ecdysone carries out this critical reproductive function in the fly, and inform the nature of hormone-behavior connections in higher organisms as well. PUBLIC HEALTH RELEVANCE: The fruit fly is an excellent animal in which to study sexual behavior, and much is known about how flies attract and court their mates. We have shown that sexual behavior in the fly depends on a hormone called ecdysone: when the adult male fly is deprived of the steroid hormone ecdysone, it begins courting other males. Determination of the mechanisms by which ecdysone controls sexual behavior will result in important clues about the normal function of steroid hormones in controlling the sexual behavior of all animals, including humans.

描述（由申请人提供）：我们将探索类固醇激素蜕皮激素对果蝇性行为的控制。果蝇模型系统已经产生了大量与人类神经系统高级功能相关的数据，包括记忆处理、睡眠、药物滥用和成瘾方面的发现。探索控制果蝇性行为的神经遗传和激素机制将增加我们对人类生活这一重要部分的理解。尽管有关求偶行为的信息非常丰富，但蜕皮激素（果蝇唯一已知的类固醇激素）对果蝇求爱的调节此前一直未知。使用蜕皮激素受体 (EcR) 基因的温度敏感等位基因（在 290°C 下不起作用），我们发现，当成年雄性的 EcR 活性受损时，雄性之间的求偶结果会升高（Ganter 等，2007）。我们使用蜕皮激素可用性基因 ecdysoneless 的 ecd1 温度敏感等位基因证实了蜕皮激素信号传导与性行为之间的关系。这些结果表明，成年雄性果蝇中的蜕皮激素信号对于调节性动机是必要的，并且成年雄性果蝇的性行为是可塑的，这两个发现以前都没有被证明过。这些结果将果蝇确立为研究激素控制行为的有效模型，其影响延伸到人类等高等生物。我们现在将描述蜕皮激素在性行为中的作用的本质。具体目标 1：描述 EcR 缺陷对已知与性行为有关的大脑区域的影响。我们将采用增强子陷阱 Gal4 策略降低大脑求爱起始区域的 EcR 功能，然后分析性行为的变化。具体目标 2：表征蜕皮激素信号亚型对女性性动机的影响。我们最近的初步结果表明，女性性动机的调节可能依赖于蜕皮激素信号传导。我们将通过一系列针对雌性交配前行为的实验来证实这一结果，并进一步验证成年雌性果蝇性动机的调节需要蜕皮激素信号传导的假设。具体目标 3：表征成人大脑蜕皮激素敏感性的发育特征。我们将通过在不同时间点和不同持续时间操纵蜕皮激素系统来表征蜕皮激素敏感性的发育生物学。我们已经将这种类固醇激素与这种易驯化的模型生物的性行为的调节联系起来，结果将帮助我们了解蜕皮激素如何在果蝇中执行这种关键的生殖功能，并了解高等生物中激素与行为联系的本质。公共健康相关性：果蝇是研究性行为的绝佳动物，人们对果蝇如何吸引和求爱的了解很多。我们已经证明，果蝇的性行为取决于一种叫做蜕皮激素的激素：当成年雄性果蝇缺乏类固醇激素蜕皮激素时，它就会开始向其他雄性求爱。确定蜕皮激素控制性行为的机制将为了解类固醇激素在控制包括人类在内的所有动物性行为中的正常功能提供重要线索。