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(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。黑腹果蝇模型系统已经产生了大量与人类神经系统更高功能相关的数据，包括在记忆处理、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学和荷尔蒙机制将增加我们对人类生活这一重要部分的理解。蜕皮激素对果蝇求偶的调节作用，尽管有丰富的求偶行为信息，但果蝇唯一已知的类固醇激素以前是未知的。使用蜕皮激素受体(ECR)基因的温度敏感等位基因(在290℃时不起作用)，我们已经表明，当成年男性的ECR活性受损时，男性-男性之间的求爱结果会增加(Ganter等人)。2007)。我们已经利用蜕皮激素可获得性基因ecd1的温度敏感等位基因证实了蜕皮激素信号与性行为的关系。这些结果表明，成年雄蝇体内的蜕皮激素信号对于调整性动机是必要的，而成年雄蝇的性行为是可塑性的，这两个发现以前都没有显示出来。这些结果建立了果蝇作为研究荷尔蒙控制行为的有效模型，其影响延伸到更高级的生物，如人类。我们现在将描述蜕皮激素在性行为中扮演的角色的性质。具体目标1：描述ECR缺陷对已知的与性行为有关的大脑区域的影响。我们将使用一种增强子陷阱Gal4策略，降低大脑中开始求爱区域的ECR功能，然后分析性行为的变化。具体目的2：研究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。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，并进一步验证蜕皮激素信号在成年雌性果蝇调控性动机中所需的假设。具体目标3：描述成人大脑对蜕皮激素敏感性的发育特征。我们将通过在不同的时间点和不同的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牵涉到这个易驯服的模式生物体的性行为调节中，结果将有助于我们理解蜕皮激素如何在苍蝇中执行这一关键的生殖功能，并揭示高等生物体中激素与行为联系的本质。与公共健康相关：果蝇是一种很好的研究性行为的动物，人们对果蝇如何吸引和追求配偶有很多了解。我们已经证明，果蝇的性行为依赖于一种名为蜕皮激素的激素：当成年雄性果蝇失去类固醇激素蜕皮激素时，它就会开始追求其他雄性果蝇。对蜕皮激素控制性行为的机制的确定将导致关于类固醇激素在控制包括人类在内的所有动物的性行为中的正常功能的重要线索。