Discovery and analysis of the C. elegans neuronal gene expression network (CeNGEN)

线虫神经元基因表达网络 (CeNGEN) 的发现和分析

• 批准号: 10608790
• 负责人: MARC HAMMARLUND
• 金额: $ 135.36万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-25 至 2027-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10608790
• 关键词: Address; Adhesions; Adult; Alternative Splicing; Atlases; Behavior; Biochemical; Brain; Caenorhabditis elegans; Catalogs; Cell Lineage; Cells; Chromosome Mapping; Communities; Complement; Complex; Data; Data Analyses; Data Set; Development; Developmental Gene; Disease susceptibility; Future; Gene Expression; Gene Expression Profiling; Gene Expression Regulation; Genes; Genetic; Genetic Transcription; Genome; Goals; Hermaphroditism; Individual; Knowledge; Learning; Logic; Maps; Molecular; Nervous System; Neuronal Differentiation; Neurons; Neurosciences; Organism; Pathway interactions; Pattern; Poly A; Polyadenylation; Process; Protein Isoforms; Proteins; Public Health; RNA; RNA Processing; RNA Splicing; Regulation; Research; Resolution; Resources; Spliced Genes; Structure; Synaptic Transmission; System; Technology; Time; Tissue-Specific Gene Expression; Transcript; Untranslated RNA; Work; adenylate; cell type; computerized tools; data mining; data tools; differential expression; dimorphism; gene product; genome-wide; insight; male; mathematical methods; model organism; neurogenetics; neuron development; novel strategies; programs; sex; sexual dimorphism; single-cell RNA sequencing; tool; transcriptome sequencing; web site; web-accessible

PROJECT SUMMARY Decades of research have established that gene expression in the nervous system is highly specific and dynamic. Different types of neurons express dramatically different genes and process RNAs to generate different isoforms. At each developmental stage, neurons express complements of RNA that together drive them along appropriate trajectories toward their ultimate fate. Similarly, in mature neurons, differential gene expression and processing are key determinants of structure, function, and disease susceptibility. However, although these phenomena are well established, a deep and broad analysis—involving genome-wide, nervous system-wide data—is not available for any organism. Ideally one would like to know, across all neuron types and all developmental stages, exactly how the genome is transcribed and processed into functional RNAs. Such detailed and complete knowledge of differential gene expression within the nervous system would help elucidate the logic and cellular mechanisms that generate neuronal diversity. Further, by comparing dynamic differential gene expression across different sexes in all neuron types, the genetic basis of neuronal sexual dimorphism can be elucidated. The C. elegans Neuronal Gene Expression Map & Network (CeNGEN) project is a multi-lab consortium with the goal of understanding gene expression in the C. elegans nervous system. Here, using a variety of RNAseq approaches, we propose to understand gene expression as neurons differentiate and acquire sexual dimorphisms for every neuron type in the C. elegans nervous system, with these Aims: Aim 1) Build and analyze a gene expression atlas for every neuron type at each stage of the developmental lineage. Aim 2) Develop a gene expression atlas across sexes, identifying sexually dimorphic gene expression in sex-shared neurons, as well as gene expression in sex-specific neurons. Aim 3) Describe splicing patterns for all genes and all neuron types, and use this information to identify all instances of differential alternative splicing. Aim 4) Generate and distribute analysis tools and data to the scientific community. CeNGEN represents a paradigmatic advance in neurogenetics, and provides a unique opportunity to elucidate the global control of neuron-specific gene expression and to relate developmental gene expression and splicing to ultimate neuronal wiring and function. CeNGEN will also serve as a resource for future studies in C. elegans neuroscience, and will provide a framework for addressing global differential gene expression in more complex nervous systems that are currently not amenable to this comprehensive approach.

项目摘要 数十年的研究已经确定，神经系统中的基因表达是高度特异的，并且 动态的。不同类型的神经元表达急剧不同的基因和过程RNA生成 不同的同工型。在每个发育阶段，神经元表达RNA的完成，共同驱动 他们沿着适当​​的轨迹朝着最终的命运。同样，在成熟的神经元中，差异基因 表达和处理是结构，功能和疾病敏感性的关键决定者。然而， 尽管这些现象已经建立得很好，但深入而广泛的分析 - 涉及全基因组，神经 全系统数据 - 任何组织都不可用。理想情况下，人们想知道，在所有神经元类型中 以及所有发育阶段，准确地将基因组转录和处理成功能性RNA。 对神经系统中差异基因表达的详细而完整的知识将有助于 阐明产生神经元多样性的逻辑和细胞机制。此外，通过比较动态 在所有神经元类型中，不同性别的差异基因表达，神经元性的遗传基础 二态性可以阐明。秀丽隐杆线虫神经元基因表达图和网络（Cengen）项目 是一个多LAB财团，目的是了解秀丽隐杆线虫神经系统中的基因表达。 在这里，使用各种RNASEQ方法，我们建议将基因表达理解为神经元 为秀丽隐杆线虫神经系统中的每种神经元类型区分并获取性二态性， 这些目的：目标1）在每个阶段的每一个神经元类型的基因表达地图集构建和分析 发展血统。目标2）跨性别发展基因表达地图集，识别性二态 性共享神经元中的基因表达以及性别特异性神经元中的基因表达。目标3）描述 所有基因和所有神经元类型的拼接模式，并使用此信息来确定所有实例 差分替代剪接。目标4）生成和分布式分析工具和数据 社区。 Cengen代表神经遗传学的范式进步，并提供了独特的机会 阐明神经特异性基因表达的全球控制并关联发育基因表达 并剪接以最终的神经元接线和功能。 Cengen还将作为未来研究的资源 在秀丽隐杆线虫神经科学中，将提供一个框架来解决全球差异基因表达 目前不适合这种综合方法的更复杂的神经系统。