Transition Support for ZEBrA, A Gene Expression Brain Atlas of the Zebra Finch

对斑胸草雀基因表达脑图谱 ZEBrA 的过渡支持

• 批准号: 9164865
• 负责人: Claudio V Mello
• 金额: $ 19.41万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-16 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9164865
• 关键词: Address; Adult; Affect; Animal Model; Area; Atlases; Base of the Brain; Behavior; Birds; Brain; Cell Nucleus; Chickens; Cognition; Cognitive; Collection; Columbidae; Communities; Comparative Study; Complex; Country; Custom; Data; Databases; Development; Disease; Ensure; Evaluation; Evolution; Funding; Funding Agency; Future; Gene Expression; Gene Structure; Genes; Genetic; Genetic Programming; Goals; Gonadal Steroid Hormones; Grant; Guinea; Health; Histology; Human; Image; In Situ; In Situ Hybridization; Individual; Institutes; Internet; Investigation; Language; Learning; Link; Maintenance; Mammals; Mental disorders; Mission; Modeling; Molecular; Molecular Profiling; Monoclonal Antibody R24; Mus; National Institute of Child Health and Human Development; National Institute of General Medical Sciences; National Institute of Mental Health; National Institute of Neurological Disorders and Stroke; National Institute on Deafness and Other Communication Disorders; Neurobiology; Neurons; Operating System; Organism; Pathway interactions; Pattern; Phase Transition; Phenotype; Physiology; Play; Preparation; Process; Processed Genes; Production; Protocols documentation; Quail; Research Personnel; Resolution; Resources; Rodent; Role; Serinus; Services; Songbirds; Source; Speech; Structure; Structure-Activity Relationship; Sturnus vulgaris; Synapses; System; United States National Institutes of Health; Update; Visit; Work; adult neurogenesis; base; bird song; brain health; cognitive skill; comparative; cost; differential expression; digital imaging; experience; human disease; improved; insight; interest; learned behavior; male; meetings; nervous system disorder; neurodevelopment; neuronal excitability; neuronal replacement; nonhuman primate; novel; selective expression; sexual dimorphism; tool; trait; usability; vocal control; vocal learning; web site; zebra finch

Project Summary Avian model organisms, including songbirds (zebra finch, canaries, starlings), chicken, quail, and pigeon have contributed much to our understanding of brain function and of disorders that affect neural development, function, and cognition. However, we still lack a clear understanding of how avian brain structures, particularly those that subserve complex learned behaviors and cognition, relate to brain structures in mammals, including humans. It is also unclear how molecular brain specializations of birds relate to those of mammals. To address these gaps, we used funding from the NINDS (R03) and NIGMS (R24) to develop the Zebra finch Brain Expression Atlas (ZEBrA), currently the only in situ hybridization database of brain gene expression for any avian species. ZEBrA is a publicly accessible website that contains >2,200 high resolution digital images of brain sections from adult male zebra finches that are aligned to a reference histological atlas, and hybridized to reveal the expression of >500 genes of relevance for brain development, physiology, plasticity, and learning, including numerous linked to human diseases or to lethal or deleterious phenotypes in rodents. Many of the patterns in ZEBrA reveal differential expression across broad brain subdivisions, previously unsuspected subdomains that cannot be visualized with conventional histology, and high enrichment in nuclei within circuits underlying specific behaviors (e.g., the system that controls vocal production and learning). These patterns have yielded novel insights into molecular specializations of major regions and of specific nuclei, including the discovery of convergent molecular specializations of vocal areas that are shared between songbirds and humans. The availability of ZEBrA has had a large impact (>4,000 users, and 35,000 page views), providing an important source of genetic and neuroanatomical data for a large number of songbird and avian researchers, many funded by the NIDCD, NIMH, NINDS or NICHD. The present proposal aims to use NIGMS's Legacy mechanism to maintain ZEBrA during a transition phase where further funding is sought to ensure the long- term availability, maintenance, and possible future expansion of this unique resource. Such studies will help to further validate the use of avian model organisms for understanding the molecular basis of brain function and disorders. Planned activities consist of regular updates to ZEBrA to ensure links to important databases and compatibility to browsers are kept up-to-date, and addition of 300 already processed genes whose images are not yet available online. Included are also plans for broad dissemination of the resource, close interactions with the community to ensure its needs are met, and evaluation to maximize ZEBrA's utility and impact. Legacy funding will facilitate the transition effort, which includes the preparation of applications to an array of NIH institutes whose stated missions are in line with ZEBrA's goals, and a more limited effort to generate brain expression data for specific genes of interest to individual users but not yet on the database, on a pay for service basis.

项目概要 鸟类模式生物，包括鸣禽（斑胸草雀、金丝雀、椋鸟）、鸡、鹌鹑和鸽子， 对我们对大脑功能和影响神经发育的疾病的理解做出了很大贡献， 功能、认知。然而，我们仍然对鸟类大脑的结构缺乏清晰的了解，特别是 那些促进复杂的学习行为和认知的因素与哺乳动物的大脑结构有关，包括 人类。目前还不清楚鸟类的分子大脑特化与哺乳动物的分子大脑特化有何关系。致地址 为了弥补这些差距，我们利用 NINDS (R03) 和 NIGMS (R24) 的资金来开发斑胸草雀大脑 表达图谱（ZEBrA），目前唯一的脑基因表达原位杂交数据库 禽类。 ZEBrA 是一个可公开访问的网站，其中包含超过 2,200 张高分辨率数字图像 成年雄性斑马雀的大脑切片与参考组织学图谱对齐，并与 揭示与大脑发育、生理学、可塑性和学习相关的 > 500 个基因的表达， 包括许多与人类疾病或啮齿动物致命或有害表型有关的疾病。许多 ZEBrA 的模式揭示了广泛的大脑分区之间的差异表达，这是以前未曾预料到的 传统组织学无法可视化的子域，以及电路内细胞核的高度富集 潜在的特定行为（例如，控制发声和学习的系统）。这些图案 对主要区域和特定核的分子专业化产生了新的见解，包括 发现鸣禽和鸟类之间共享的发声区域的趋同分子特化 人类。 ZEBrA 的可用性产生了巨大影响（超过 4,000 位用户和 35,000 次页面浏览），提供了 大量鸣禽和鸟类研究人员的遗传和神经解剖数据的重要来源， 许多项目由 NIDCD、NIMH、NINDS 或 NICHD 资助。本提案旨在利用 NIGMS 的遗产 在过渡阶段维持 ZEBrA 的机制，寻求进一步的资金以确保长期 这一独特资源的期限可用性、维护和未来可能的扩展。此类研究将有助于 进一步验证鸟类模型生物体在理解大脑功能的分子基础方面的用途 失调。计划的活动包括定期更新 ZEBrA，以确保与重要数据库的链接和 与浏览器的兼容性保持最新，并添加了 300 个已处理的基因，其图像 尚未在线提供。还包括广泛传播资源、与 社区以确保其需求得到满足，并进行评估以最大限度地提高 ZEBrA 的效用和影响。遗产 资金将促进过渡工作，其中包括准备向一系列 NIH 的申请 其既定使命符合 ZEBrA 目标的机构，以及更有限的大脑生成努力 个人用户感兴趣但尚未进入数据库的特定基因的表达数据，需要付费 服务基础。