Ecdysone modulation of sexual behavior in Drosophila melanogaster

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。黑腹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、药物滥用和成瘾的发现。探索控制果蝇性行为的神经遗传学和激素机制将增加我们对人类生活中这一重要部分的理解。尽管关于果蝇求偶行为的信息丰富，但果蝇唯一已知的类固醇激素蜕皮激素对果蝇求偶行为的调节在以前是未知的。利用蜕皮激素受体（EcR）基因的一个温度敏感等位基因（在290℃时不起作用），我们已经证明，当成年雄性EcR活性受损时，雄性之间的求爱结果会升高（Ganter et al. 2007）。我们利用蜕皮激素可利用性基因的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，成年雄性的蜕皮激素信号对于性动机的调节是必要的，并且成年雄性果蝇的性行为是可塑的，这两项发现之前都没有被证明。这些结果确立了果蝇作为研究激素控制行为的有效模型，并将其应用于人类等高等生物。现在我们将描述蜕皮激素在性行为中的作用。具体目标1：表征EcR缺陷对已知参与性行为的大脑区域的影响。我们将采用增强子诱捕Gal4策略，减少大脑求爱起始区域的EcR功能，然后分析性行为的变化。特异性目的2：表征蜕皮激素信号畸形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。我们将通过一系列关于雌性预交配行为的实验来证实这一结果，并进一步验证蜕皮激素信号是调节成年雌性果蝇性动机所必需的假设。具体目的3：表征成人大脑蜕皮激素敏感性的发育特征。我们将通过在不同的时间点和不同的持续时间操纵蜕皮激素系统来描述蜕皮激素敏感性的发育生物学特征。我们已经将这种类固醇激素与这种可塑性模式生物的性行为调节联系在一起，研究结果将帮助我们理解蜕皮激素是如何在果蝇中实现这种关键的生殖功能的，并告知高等生物中激素-行为联系的本质。公共卫生相关性：果蝇是研究性行为的极好动物，关于果蝇如何吸引和追求配偶，我们已经知道了很多。我们已经证明，苍蝇的性行为取决于一种叫做蜕皮激素的激素：当成年雄性苍蝇被剥夺了类固醇激素蜕皮激素时，它就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类固醇激素在控制包括人类在内的所有动物的性行为方面的正常功能提供重要线索。

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.