Chromatin-based encoding of sex differentiation of neurons

项目摘要 许多物种的动物发育为两种解剖学性别， 行为。跨进化枝，性别决定程序下游的主调节转录因子 通过改变神经元数量，“切换”不同的大脑区域和神经元， 解剖学和连通性。在昆虫中，雄性特异性转录因子Fruitless（FruM）在昆虫的生长过程中是必需的。 交配行为的发展，包括对同种雌性处女的先天求爱行为。弗鲁姆 改变了组成电路的神经元的数量、解剖结构和连通性。然而，如何FruM 在发育过程中执行这些完全不同的基因组程序， 选择，以及发展景观如何限制FruM的功能仍然知之甚少。到 为了解决这些问题，我们建议研究FruM如何建立和维持神经元的变化， 通过改变组成神经元的调节元件的染色质可及性来改变求偶回路。我们 将研究1）FruM对神经发育基因在电路连接中的抑制活性， 功能，以及2）确定FruM如何以及何时作用于染色质景观以进行硬连线求爱 行为在这个提议中，我们将阐明FruM的分子和电路功能， 配偶选择和求偶行为在电路的发展。 本F31提案描述了申请人的全面培训和指导计划， 博士他是密歇根大学细胞和分子生物学项目的候选人。申请人将 参加严格的教学和实验室培训课程，由她的赞助商，博士监督。乔西 Clowney和共同赞助人Scott Barolo博士她将获得多学科论文的额外支持 委员会和密歇根大学的扩展神经科学社区。该培训计划包括 广泛而严格的分子遗传学和系统神经科学实验室培训，以及指导 有机会从事科学写作，演讲和资助申请。这个项目的最终目标 建议是最好的位置申请人独立和生产的科学生涯。

Project Summary Animals of many species develop as two anatomic sexes that perform distinct and complex social behaviors. Across clades, master regulator transcription factors downstream of sex determination programs “switch” distinct brain regions and neurons involved in sex-typical behaviors by altering neuron number, anatomy, and connectivity. In insects, the male-specific transcription factor Fruitless (FruM) is required during development for mating behaviors, including innate courtship behavior towards conspecific female virgins. FruM changes the number, anatomy and connectivity of neurons which comprise the circuit. However, how FruM executes these disparate genomic programs during development, when these programs hard-wire mate choice, and how the developmental landscape constrains the function of FruM is still poorly understood. To address these questions, we propose to investigate how FruM establishes and maintains changes in neurons of the courtship circuit by altering chromatin accessibility of regulatory elements across constituent neurons. We will investigate 1) the repressive activities of FruM on neurodevelopmental genes in circuit connectivity and function, and 2) determine how and when FruM acts on the chromatin landscape to hard-wire courtship behavior. In this proposal, we will thereby elucidate the molecular and circuit function of FruM that hard-wires mate choice and courtship behavior during development of the circuit. This F31 proposal describes a comprehensive training and mentorship program for the applicant, a Ph.D. candidate in the Cellular and Molecular Biology program at the University of Michigan. The applicant will participate in a rigorous didactic and laboratory training curriculum, supervised by her sponsor, Dr. E. Josie Clowney, and co-sponsor, Dr. Scott Barolo. She will receive additional support from a multi-disciplinary thesis committee and the extended neuroscience community at the University of Michigan. This training plan includes extensive and rigorous molecular genetics and systems neuroscience laboratory training, as well as mentored opportunities to engage in scientific writing, presentations, and grant applications. The ultimate goal of this proposal is to best position the applicant for an independent and productive scientific career.