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.

项目摘要 鸟类模型生物，包括鸣禽（斑马雀，金丝雀，八哥），鹦鹉，鸡，鹌鹑和 鸽子为我们对影响神经的脑功能和疾病的理解做出了很大的贡献 发展，功能和认知。此外，许多鸟类越来越被认为 拥有能够具有高级认知和学习技能的大脑扩大，甚至超越了 那些在哺乳动物中。尽管有这些贡献，我们仍然对分子大脑的方式缺乏清晰的了解 鸟类中的组织与包括人类在内的哺乳动物相比。为了解决这个差距，我们利用了 来自Ninds和Nigms的资源建设资金开发斑马雀科表达大脑图集 （斑马），目前是任何鸟类物种的脑基因表达的原位杂交数据库。 Zebra是一个公开访问的网站，其数据库包含> 3,500个高分辨率的数字图像 成年男性斑马雀科的脑部切片与参考组织学地图集排列，并杂交 揭示了> 720个与大脑发育，生理，可塑性和 声带学习。值得注意的是，这些基因中有近200个与语音和/或神经疾病有关 人类和/或构成人声生产的类似大脑区域的共享分子专业 和在鸟类和人类中学习。斑马中的许多表达模式先前也揭示了 常规组织学技术不可见的未陈化子域以及富集 在基于特定行为的电路中的离散核中（例如声音产生和学习）。尽管 这些发现，尚未对斑马数据库进行定量分析，这已阻碍 我们使用哺乳动物具有相似资源进行准确比较分析的能力（例如，艾伦 研究所的老鼠大脑图集-MBA）。我们在这里建议使用图像分析方法提取等效 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 主要大脑区域的轮廓和声带控制和学习电路的专门核，后者A 与人类言语和语言高相关的认知特征。斑马和MBA数据也将是 与得出有关禽流和哺乳动物大脑如何相关或分子差异的见解相比。这样的见解 将有助于进一步验证使用禽类作为信息的模型生物，以理解 大脑功能和认知能力的分子基础，以及高脑疾病的遗传基础 与人类有关。

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.

• 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