CAREER: How the Dissatisfaction nuclear receptor regulates Drosophila courtship behavior

神经系统的形成能够整合外部输入，做出决定，并协调运动输出，这对健康的生活至关重要。为了揭示指导这一过程的基本原理，该项目调查了果蝇的发育基因如何控制它们的生殖行为和神经系统发育。该项目涉及应用尖端遗传和神经科学工具来确定与行为相关的神经元及其在关键神经回路中的位置，揭示基因如何促进回路的发育，回路内表达基因的神经元的连接及其功能，以及哪些基因对行为输出重要，由发育基因调节。该项目还包括一项教育计划，将高中生和本科生纳入研究活动。一个基于发现的项目被引入到费城地区的两所高中，其中一所的学生来自以低收入家庭为主的家庭。该项目的这一方面考察了真实的研究经验是否可以提高高中生对STEM学科的态度。这项工作调查了果蝇性行为背后的基因和神经网络，重点是不满意(Dsf)基因。DSF编码一种无尾的发育核受体，这种突变会导致两性特定的求爱和生育缺陷。初步工作将大多数DSF控制的表型映射到极其稀少的中间神经元数量(即，3+)。这个项目测试了这样的假设，即dsf通过调节目标基因的表达来影响行为，这些目标基因指定了用于求爱的离散神经回路元件的功能和连通性。该项目包括描绘已识别的中间神经元在控制求爱的回路中的位置；确定dsf如何促进神经发育和回路连接；以及识别dsf转录调节的基因。这项工作的一个关键成果是在dsf的活动、其影响的神经回路的发展和功能以及求爱行为之间建立了因果联系。此外，这项工作将为理解DSF如何与神经元内或神经元之间的其他性别分化调控基因一起作用以改变行为模式奠定基础。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

The formation of a nervous system capable of integrating outside inputs, making decisions, and coordinating motor outputs is critical for a healthy life. To uncover basic principles that guide this process, this project investigates how a developmental gene in fruit flies controls their reproductive behaviors and nervous system development. The project involves the application of cutting-edge genetic and neuroscience tools to identify the behaviorally-relevant neurons and their location within the key neural circuit, uncover how the gene contributes to the development of the circuit, the connections of the gene-expressing neurons within the circuit and their function, and what genes important for the behavioral output are regulated by the developmental gene. This project also includes an education plan that integrates high school and undergraduate students into the research activities. A discovery-based project is introduced to two Philadelphia-area high schools, including one with students from predominantly low-income households. This aspect of the project examines whether authentic research experiences can enhance the attitudes of high school students towards STEM disciplines. This work investigates the gene and neural networks that underlie sexual behavior in Drosophila focusing on the dissatisfaction (dsf) gene. Dsf encodes a tailless-like developmental nuclear receptor, mutations in which cause sex-specific courtship and fertility defects in both sexes. Preliminary work mapped most DSF-controlled phenotypes to an exceedingly sparse number (i.e., 3+) of interneurons. This project tests the hypothesis that dsf contributes to behavior by regulating the expression of target genes that specify the function and connectivity of discrete neural circuit elements for courtship. The project includes delineation of the position of the identified interneurons in the circuits that control courtship; determination of how dsf contributes to neurodevelopment and circuit connectivity; and identification of the genes that dsf transcriptionally regulates. A key outcome of this work is the establishment of causal links between the activity of dsf, the development and function of the neural circuits it influences, and courtship behavior. Additionally, this work will set the stage for understanding how dsf acts with other sexual differentiation regulatory genes either within or between neurons to pattern behavior.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.