Molecular profiling of the zebra finch brain

斑胸草雀大脑的分子分析

• 批准号: 10062755
• 负责人: Claudio V Mello
• 金额: $ 15.4万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10062755
• 关键词: Address; Adult; Affect; Algorithms; Anatomy; Animal Model; Apraxias; Architecture; Area; Atlases; Behavior; Biology; Birds; Brain; Brain Diseases; Brain imaging; Brain region; Cell Density; Cell Nucleus; Cell Size; Cells; Chickens; Cognition; Cognitive; Columbidae; Comparative Study; Complex; Corpus striatum structure; Data; Data Set; Databases; Development; Disease; Evolution; Expressed Sequence Tags; FOXP2 gene; Family Psittacidae; Finches; Funding; Gene Expression; Gene Expression Profile; Genes; Genetic; Genome; Goals; Gonadal Steroid Hormones; Health; Histologic; Histological Techniques; Human; Hybrids; Image; Image Analysis; Impairment; In Situ Hybridization; Institutes; Knowledge; Language; Language Development; Language Disorders; Learning; Learning Skill; Link; Mammals; Mental disorders; Methods; Mind; Molecular; Molecular Profiling; Monoclonal Antibody R24; Motor; Mus; Mutation; National Institute of General Medical Sciences; National Institute of Neurological Disorders and Stroke; Neurobiology; Neurons; Nuclear; Outcome; Pattern; Phase; Physiology; Positioning Attribute; Principal Component Analysis; Production; Property; Quail; Resolution; Resources; Rodent; Sampling; Serinus; Sleep; Songbirds; Speech; Speech Disorders; Structure; Structure-Activity Relationship; Sturnus vulgaris; Stuttering; System; Transcript; United States National Institutes of Health; Vertebrates; adult neurogenesis; base; behavioral phenotyping; cDNA Library; cell type; cognitive function; cognitive skill; comparative; differential expression; digital imaging; information model; insight; interest; male; nervous system disorder; neurodevelopment; nonhuman primate; novel; relating to nervous system; sexual dimorphism; stem; trait; vocal control; vocal learning; web site; zebra finch

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.

项目概要 鸟类模式生物，包括鸣禽（斑胸草雀、金丝雀、椋鸟）、鹦鹉、鸡、鹌鹑和 鸽子为我们了解大脑功能和影响神经的疾病做出了很大贡献 发育、功能和认知。此外，许多鸟类群体越来越被认为是 拥有扩大的大脑，具有可以媲美甚至超越的高级认知和学习技能 那些在哺乳动物中。尽管有这些贡献，我们仍然对分子大脑如何 鸟类的组织与包括人类在内的哺乳动物的组织相比。为了解决这个差距，我们利用 NINDS 和 NIGMS 提供资源建设资金，用于开发斑胸草雀表达脑图谱 （ZEBrA），目前最大的鸟类大脑基因表达原位杂交数据库。 ZEBrA 是一个可公开访问的网站，其数据库包含超过 3,500 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、可塑性和相关性相关的 > 720 个基因的全脑表达 声乐学习。值得注意的是，其中近 200 个基因与言语和/或神经障碍有关。 人类，和/或构成用于发声的类似大脑区域的共享分子特化 以及鸟类和人类的学习。 ZEBrA 中的许多表达模式之前也已揭示 使用传统组织学技术以及富集技术看不到的未知子域 存在于构成特定行为（例如发声和学习）的回路内的离散核中。尽管 这些发现尚未对 ZEBrA 数据库进行定量分析，这阻碍了 我们有能力对哺乳动物的类似资源进行准确的比较分析（例如 Allen 研究所的小鼠大脑图谱 - MBA）。我们在这里建议使用图像分析方法来提取等效的 来自两个数据库的区域基因表达数据。芬奇的结果将定义区域分子 主要大脑区域和声音控制和学习电路的专门核的轮廓，后者是 与人类言语和语言高度相关的认知特征。 ZEBrA 和 MBA 数据也将 进行比较，以深入了解鸟类和哺乳动物的大脑如何在分子上相关或分歧。这样的见解 将有助于进一步验证鸟类物种作为信息模型生物的用途，以了解 大脑功能和认知技能的分子基础，以及高智商脑部疾病的遗传基础 与人类的相关性。

项目成果

Cell type specializations of the vocal-motor cortex in songbirds.

• DOI: 10.1016/j.celrep.2023.113344
• 发表时间: 2023-11-28
• 期刊: Cell reports
• 影响因子: 8.8

Emergence of sex-specific transcriptomes in a sexually dimorphic brain nucleus.

• DOI: 10.1016/j.celrep.2022.111152
• 发表时间: 2022-08-02
• 期刊: CELL REPORTS
• 影响因子: 8.8
• 作者: Friedrich, Samantha R.;Nevue, Alexander A.;Andrade, Abraao L. P.;Velho, Tarciso A. F.;V. Mello, Claudio
• 通讯作者: V. Mello, Claudio

False gene and chromosome losses in genome assemblies caused by GC content variation and repeats.

• DOI: 10.1186/s13059-022-02765-0
• 发表时间: 2022-09-27
• 期刊: Genome biology
• 影响因子: 12.3

ZEBrA: Zebra finch Expression Brain Atlas-A resource for comparative molecular neuroanatomy and brain evolution studies.

斑马：斑马雀科表达大脑Atlas-A比较分子神经解剖学和脑进化研究的资源。

• DOI: 10.1002/cne.24879
• 发表时间: 2020-08
• 期刊: The Journal of comparative neurology
• 作者: Lovell PV;Wirthlin M;Kaser T;Buckner AA;Carleton JB;Snider BR;McHugh AK;Tolpygo A;Mitra PP;Mello CV
• 通讯作者: Mello CV