Molecular profiling of the zebra finch brain

项目摘要 鸟类模式生物，包括鸣禽(斑马雀、金丝雀、八哥)、鹦鹉、鸡、鹌鹑和 鸽子对我们了解大脑功能和影响神经的疾病做出了很大贡献 发展、功能和认知。此外，许多鸟类群体正越来越多地被认为是 拥有庞大的大脑，能够拥有可与之匹敌甚至超越的高级认知和学习技能 在哺乳动物身上。尽管有这些贡献，我们仍然缺乏对分子脑如何 鸟类的组织结构与包括人类在内的哺乳动物的组织结构相比。为了解决这一差距，我们利用 NINDS和NIGMS的资源建设资金用于开发斑雀表达脑图谱 斑马)，目前是所有鸟类中最大的脑基因表达的原位杂交数据库。 斑马是一个可公开访问的网站，其数据库包含&gt；3,500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 揭示与脑发育、生理、可塑性和脑发育相关的&gt；720基因在整个大脑中的表达。 声乐学习。值得注意的是，其中近200个基因与语言和/或神经障碍有关 人类，和/或构成发声的相似大脑区域的共享分子专门化 以及在鸟类和人类身上的学习。斑马的许多表达模式也在以前揭示过 用常规组织学技术看不到的意外亚域以及富集物 在构成特定行为(例如，发声和学习)的回路内的离散核团中。尽管 这些发现，斑马数据库的量化分析还没有进行，这就阻碍了 我们能够与来自哺乳动物(例如Allen)的类似资源进行准确的比较分析 研究所的老鼠脑地图集(MBA)。我们建议使用图像分析方法来提取等价物 来自两个数据库的区域基因表达数据。芬奇的研究结果将定义区域分子 发声控制和学习回路的主要脑区和特殊核团的轮廓，后者是 与人类言语和语言高度相关的认知特征。斑马和MBA数据也将是 而是深入了解鸟类和哺乳动物的大脑在分子上是如何联系或分化的。这样的洞察力 将有助于进一步验证将鸟类作为信息丰富的模式生物的使用，以了解 脑功能和认知技能的分子基础，以及高血压性脑病的遗传基础 与人类的关联性。

Project Summary Avian model organisms, including songbirds (zebra finches, canaries, starlings), parrots, chicken, quail, and pigeons have contributed much to our understanding of brain function and disorders that affect neural development, function, and cognition. Furthermore, many bird groups are being increasingly recognized as having enlarged brains that are capable of advanced cognitive and learning skills that rival and even surpass those in mammals. Despite these contributions, we still lack a clear understanding of how the molecular brain organization in birds compares to that in mammals, including humans. To address this gap, we utilized resource building funds from the NINDS and NIGMS to develop the Zebra finch Expression Brain Atlas (ZEBrA), currently the largest in situ hybridization database of brain gene expression for any avian species. ZEBrA is a publicly accessible website with a database containing >3,500 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 brain-wide expression of >720 genes of relevance for brain development, physiology, plasticity, and vocal learning. Notably, nearly 200 of these genes have been linked to speech and/or neural disorders in humans, and/or constitute shared molecular specializations of analogous brain regions for vocal production and learning in birds and humans. Many expression patterns in ZEBrA have also revealed previously unsuspected subdomains that are not visible with conventional histological techniques, as well as enrichments in discrete nuclei within circuits that underlie specific behaviors (e.g., vocal production and learning). Despite these findings, a quantitative analysis of the ZEBrA database has not yet been performed, which has hindered our ability to perform accurate comparative analyses with similar resources from mammals (e.g. Allen Institute's Mouse Brain Atlas - MBA). We propose here to use image analysis methods to extract equivalent regional gene expression data from both databases. The outcomes in finch will define regional molecular profiles of major brain areas and specialized nuclei of the vocal control and learning circuitry, the latter a cognitive trait of high relevance to human speech and language. The ZEBrA and MBA data will also be compared to derive insights into how avian and mammalian brains relate or diverge molecularly. Such insights will help to further validate the use of avian species as informative model organisms for understanding the molecular basis of brain function and cognitive skills, as well as the genetic basis of brain disorders of high relevance to humans.