CAREER: How the Dissatisfaction nuclear receptor regulates Drosophila courtship behavior

事业：不满核受体如何调节果蝇求爱行为

• 批准号: 1845673
• 负责人: Troy Shirangi
• 金额: $ 64.53万
• 依托单位: Villanova University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-06-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1845673&HistoricalAwards=false
• 关键词: CAREER; How; Dissatisfaction; nuclear; receptor

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.

神经系统的形成能够整合外部输入，做出决定和协调运动输出对于健康的生活至关重要。 为了揭示指导这一过程的基本原则，该项目研究了果蝇中的发育基因如何控制其生殖行为和神经系统发育。 该项目涉及尖端遗传和神经科学工具的应用，以识别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，回路内基因表达神经元的连接及其功能，以及发育基因对行为输出的重要性。 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。 在费城地区的两所高中引入了一个以发现为基础的项目，其中一所高中的学生主要来自低收入家庭。 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。这项工作调查的基因和神经网络，在果蝇性行为的不满（dsf）基因为重点。Dsf编码一种类似无尾的发育核受体，其突变导致两性的性别特异性求偶和生育缺陷。初步工作将大多数DSF控制的表型映射到非常稀疏的数量（即，3+）的中间神经元。这个项目测试了dsf通过调节目标基因的表达来促进行为的假设，这些目标基因指定了求偶的离散神经回路元件的功能和连接。该项目包括描绘已识别的中间神经元在控制求偶回路中的位置;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建立了dsf活动、其影响的神经回路的发育和功能以及求爱行为之间的因果关系。 此外，这项工作将为理解dsf如何与其他性分化调控基因在神经元内或之间起作用以形成行为模式奠定基础。该奖项反映了NSF的法定使命，并被认为值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估来支持。

项目成果

The development of sex differences in the nervous system and behavior of flies, worms, and rodents

苍蝇、蠕虫和啮齿动物的神经系统和行为中性别差异的发展

• DOI: 10.1016/j.ydbio.2021.01.010
• 发表时间: 2021
• 期刊: Developmental Biology
• 影响因子: 2.7
• 作者: Meeh, Kristen L.;Rickel, Clare T.;Sansano, Alexander J.;Shirangi, Troy R.
• 通讯作者: Shirangi, Troy R.

Developmental remodeling repurposes larval neurons for sexual behaviors in adult Drosophila

• DOI: 10.1016/j.cub.2024.01.065
• 发表时间: 2024-03-25
• 期刊: CURRENT BIOLOGY
• 影响因子: 9.2
• 作者: Diamandi，Julia A.;Duckhorn，Julia C.;Shirangi，Troy R.
• 通讯作者: Shirangi，Troy R.

Regulation of Drosophila courtship behavior by the Tlx/tailless-like nuclear receptor, dissatisfaction

• DOI: 10.1016/j.cub.2022.02.031
• 发表时间: 2022-02
• 期刊: Current Biology
• 影响因子: 9.2
• 作者: Julia C. Duckhorn;J. Cande;Mary C. Metkus;Hyeop Song;Sofia Altamirano;D. Stern;Troy R. Shirangi