Genes Underlying Reproductive Behavior and Physiology

描述（由申请人提供）：复杂的行为要求动物能够感知外部环境，整合信息并以适当的运动输出做出反应。因此，理解复杂行为是如何被指定的，需要对这些行为背后的神经回路的发展以及生理变化如何指导成人行为输出的综合理解。黑腹果蝇是研究神经发育遗传基础和复杂行为遗传基础的首选模型系统。先进的分子遗传学工具，加上细胞成像方法可用于研究果蝇的行为和神经发育。此外，还有一些复杂行为的遗传决定因素的知识，包括那些指定生殖行为所需的神经基质。果蝇雄性求偶行为是性别决定层次下游的遗传特异性行为，性别决定层次是一个前mRNA剪接级联，最终产生由无结果和doubletex编码的性别特异性转录因子。分子遗传学研究表明，雄性求偶行为的几乎所有方面都需要无果。其中表达雄性特有的fruitless产物的神经元已经被鉴定出来，并被证明是雄性求偶行为能力的基础。这种知识的汇合男性特定的转录因子，指定的行为，神经回路的识别重要的行为和复杂的分子遗传学工具，可用于果蝇基因组和细胞成像研究提供了前所未有的机会，以深入了解复杂的行为。这项拨款提案的目的是研究神经系统中的性二态性在发育过程中是如何被指定的，以及经验依赖性的变化是如何在成年阶段被编码到神经系统中的。这些研究将为理解包括人类在内的其他动物行为的遗传基础提供基础。 公共卫生相关性：我们将开发果蝇作为分析复杂行为遗传规范的模型。该研究将提供有关神经回路如何使用分子遗传学，基因组学和细胞成像方法在遗传水平上指定和功能的机制见解，这对于理解其他生物体（包括人类）行为的神经基础至关重要。

DESCRIPTION (provided by applicant): Complex behaviors require that an animal can sense the external environment, integrate information and respond with the appropriate motor output. Therefore, understanding how complex behaviors are specified requires an integrated understanding of the development of the neural circuits that underlie these behaviors, as well as how physiological changes direct the adult behavioral output. Drosophila melanogaster has been a premiere model system for the study of the genetic basis of neural development and more recently for the genetic basis of complex behavior. Sophisticated molecular-genetic tools, coupled with cell imaging approaches are available for the study of Drosophila behavior and neural development. Furthermore, there is knowledge of the genetic determinants of some complex behaviors, including those that specify the neural substrates necessary for reproductive behaviors. Drosophila male courtship behaviors are genetically specified behaviors that are downstream of the sex determination hierarchy, a pre-mRNA splicing cascade that culminates in the production of sex-specific transcription factors encoded by fruitless and doublesex. Molecular-genetic studies have shown that fruitless is both necessary and sufficient for nearly all aspects of male courtship behaviors. The neurons in which the male-specific products of fruitless are expressed have been identified and shown to underlie the capacity for male courtship behaviors. This confluence of knowledge of male-specific transcription factors that specify behaviors, the identification of the neural circuit important for the behavior and the sophisticated molecular-genetic tools available for Drosophila genomic and cell imaging studies provides an unprecedented opportunity to gain insight into complex behaviors. The aims of this grant proposal are to study how sexual dimorphism in the nervous system is specified during development and how experience-dependent changes are encoded into the nervous system at adult stages. These studies will provide a foundation for understanding the genetic basis of behaviors in other animals, including humans. PUBLIC HEALTH RELEVANCE: We will develop Drosophila as a model for analysis of the genetic specification of complex behaviors. The research will provide mechanistic insight regarding how neural circuits are specified and function at the genetic level using molecular-genetic, genomic and cell imaging approaches, which is critical for understanding the neural basis of behavior in other organisms, including humans.