Chromatin-based encoding of sex differentiation of neurons

基于染色质的神经元性别分化编码

基本信息

批准号：
10603287
负责人：
Margarita Brovkina
金额：
$ 4万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-01-01 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10603287
关键词：
Address Adult Afferent Neurons Aggressive behavior Anatomy Animals Applications Grants Axon Behavior Behavioral Bioinformatics Biological Assay Biological Metamorphosis Brain Brain region Caring Cells Cellular biology Chimeric Proteins Chromatin Chromatin Remodeling Factor Communities Complex Courtship DNA Binding Domain Data Development Disparate Doctor of Philosophy Drosophila genus Drosophila melanogaster Educational Curriculum Enhancers Event Female Gene Expression Genes Genetic Genetic Enhancer Element Genetic Transcription Genomics Goals Growth Insecta Label Link Maps Men&apos s Role Mentors Mentorship Michigan Molecular Molecular Biology Molecular Genetics Morphology Mutate Neuroanatomy Neuronal Differentiation Neurons Neurosciences Organism Output Partner in relationship Pathway interactions Pattern Physiology Play Population Positioning Attribute Productivity Proteins Regulator Genes Regulatory Element Reporter Reporting Repression Role Sex Differentiation Sexual Reproduction Social Behavior Specific qualifier value Specificity Synapses System Testing Training Universities Work Writing axon guidance brain size career cell type gene repression in vivo laboratory experience male mating behavior model organism multidisciplinary neural neural circuit neuronal circuitry offspring programs recruit sensory input sex sex determination sexual dimorphism synaptogenesis tool transcription factor

项目摘要

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.

项目概要许多物种的动物发育成两种解剖性别，表现出独特而复杂的社会跨进化枝，掌握性别决定程序下游的调节转录因子。通过改变神经元数量“切换”参与典型性别行为的不同大脑区域和神经元，在昆虫中，雄性特有的转录因子 Fruitless (FruM) 在昆虫的发育过程中是必需的。交配行为的发展，包括对同种雌性处女的先天求爱行为。然而，FruM 改变了组成电路的神经元的数量、解剖结构和连接性。在开发过程中执行这些不同的基因组程序，当这些程序硬连线配合时选择，以及发展格局如何限制 FruM To 的功能仍然知之甚少。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形成求爱回路。将研究 1) FruM 对回路连接中神经发育基因的抑制活性和功能，以及 2) 确定 FruM 如何以及何时作用于染色质景观以实现硬线求爱在本提案中，我们将阐明硬连线的 FruM 的分子和电路功能。电路发育过程中的配偶选择和求偶行为。此 F31 提案描述了针对申请人的全面培训和指导计划，密歇根大学细胞和分子生物学项目的博士候选人参加严格的教学和实验室培训课程，由她的赞助商 E. Josie 博士监督克劳尼和共同发起人斯科特·巴罗洛博士将获得多学科论文的额外支持。该培训计划包括委员会和密歇根大学扩展神经科学界。广泛而严格的分子遗传学和系统神经科学实验室培训，以及指导参与科学写作、演示和资助申请的机会这是其最终目标。提案旨在为申请人提供独立且富有成效的科学职业的最佳定位。