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.

项目摘要许多物种的动物作为两种表现独特而复杂的社交的解剖性别发展行为。在整个进化枝之间，主管确定计划下游的主要调节器转录因子通过改变神经元数来参与性典型行为的“开关”不同的大脑区域和神经元，解剖和连通性。在昆虫中，需要在昆虫中毫无结果的转录因子（frum）交配行为的发展，包括对特定女性处女的先天求爱行为。弗鲁姆改变构成电路的神经元的数量，解剖和连通性。但是，多么烦恼在开发过程中，当这些程序硬婚伴侣时，执行这些不同的基因组程序选择，以及发展景观如何限制FRUM的功能仍然很少理解。到解决这些问题，我们建议调查FRUM如何建立和维护神经元的变化通过改变组成神经元调节元素的染色质可及性，求爱巡回赛。我们将研究1）FRUM对电路连通性神经发育基因的反射活性和功能，以及2）确定FRUM在染色质景观上的如何以及何时作用行为。在此提案中，我们将阐明硬线的分子和电路功能巡回演出期间的伴侣选择和求爱行为。该F31提案描述了针对申请人的全面培训和指导计划博士密歇根大学的细胞和分子生物学计划中的候选人。申请人将参加由她的赞助商E. Josie博士监督的严格的教学和实验室培训课程 Clowney和共同赞助商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从事科学写作，演讲和赠款应用的机会。最终目标提案是最好地定位独立和产品科学生涯的申请人。