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

项目摘要 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， 对我们理解大脑功能和影响神经发育的疾病做出了很大贡献， 功能和认知。然而，我们仍然缺乏对鸟类大脑结构的清晰理解， 那些有助于复杂的学习行为和认知的，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脑特化与哺乳动物的分子脑特化之间的关系。解决 为了填补这些空白，我们利用NINDS（R03）和NIGMS（R24）的资金开发了斑胸草雀大脑 表达图谱（ZEBrA），目前唯一的大脑基因表达的原位杂交数据库， 鸟类物种。ZEBrA是一个可公开访问的网站，包含超过2，200张高分辨率数字图像， 将成年雄性斑胸草雀的脑切片与参考组织学图谱对齐，并与 揭示了与大脑发育、生理学、可塑性和学习相关的超过500个基因的表达， 包括许多与人类疾病或啮齿类动物的致命或有害表型有关的疾病。许多 ZEBrA的模式揭示了广泛的脑分区的差异表达，这是以前未被怀疑的 常规组织学无法观察到的子域，以及回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）。这些模式 对主要区域和特定细胞核的分子特化产生了新的见解，包括 发现鸣禽之间共有的发声区的会聚分子特化， 人类ZEBrA的可用性产生了很大的影响（> 4，000个用户和35，000个页面浏览量），提供了一个 是大量鸣禽和鸟类研究人员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 在过渡阶段寻求进一步资金，以确保长期 这一独特资源的长期可用性、维护以及未来可能的扩展。这些研究将有助于 进一步验证使用鸟类模式生物来理解脑功能的分子基础， 紊乱计划的活动包括定期更新ZEBrA，以确保与重要数据库的链接， 与浏览器的兼容性保持最新，并增加了300个已经处理过的基因，其图像 尚未在网上提供。其中还包括广泛传播资源的计划， 社区，以确保其需求得到满足，并评估，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，其中包括准备申请到一系列国家卫生研究院 研究所的既定任务符合ZEBRA的目标，以及更有限的努力，以产生大脑 个人用户感兴趣但尚未在数据库中的特定基因的表达数据，付费 服务基础。

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.