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(斑马雀、金丝雀、八哥)、鸡、鹌鹑和鸽子 对我们了解大脑功能和影响神经发育的疾病有很大贡献， 功能和认知。然而，我们仍然缺乏对鸟类大脑结构的清楚了解，特别是 那些辅助复杂的习得行为和认知的，与哺乳动物的大脑结构有关，包括 人类。鸟类的分子大脑特化与哺乳动物的分子大脑特化之间的关系也不清楚。致信地址 为了弥补这些空白，我们利用NINDS(R03)和NIGMS(R24)的资金来开发斑雀的大脑 表达图谱(Zebra)，目前唯一的脑基因表达的原位杂交数据库 鸟类。斑马是一个可公开访问的网站，其中包含&gt；2,200张高分辨率数字图像 成年雄性斑马雀的脑切片，与参考组织图谱一致，并与 揭示与大脑发育、生理、可塑性和学习相关的&gt；500基因的表达， 包括许多与人类疾病或啮齿动物致死或有害表型有关的基因。许多人 斑马的模式显示了不同脑区的差异表达，这是以前没有预料到的 用常规组织学不能看到的亚区，以及回路内细胞核的高度浓缩 潜在的特定行为(例如，控制发声和学习的系统)。这些模式 对主要区域和特定核的分子专门化产生了新的见解，包括 鸣禽和鸣禽共同发声区域的趋同分子特化的发现 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 大量鸣禽和鸟类研究人员遗传和神经解剖学数据的重要来源， 许多项目由NIDCD、NIMH、NINDS或NICHD提供资金。目前的提案旨在利用NIGMS的遗产 在过渡阶段维持斑马线的机制，在过渡阶段寻求进一步的资金以确保长期的- 这一独特资源的期限可获得性、维护和未来可能的扩展。这样的研究将有助于 进一步验证使用禽类模型生物来理解大脑功能和 精神错乱。计划的活动包括对Zebra的定期更新，以确保与重要数据库和 与浏览器的兼容性保持最新，并添加了300个已经处理过的基因，其图像是 目前还没有在网上提供。还包括广泛传播资源的计划，与 社区确保其需求得到满足，并进行评估，以最大限度地提高斑马的实用性和影响力。遗赠 资金将促进过渡工作，其中包括准备向一系列国家卫生研究院提出申请 其宣称的使命与斑马的目标一致的机构，以及更有限的培养大脑的努力 个人用户感兴趣的特定基因的表达数据，但尚未在数据库中，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.