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 几十年的研究已经证实，神经系统中的基因表达是高度特异性的， 动态的不同类型的神经元表达截然不同的基因和过程RNA， 不同的同种型在每个发育阶段，神经元表达RNA的互补物， 他们沿着合适的轨迹走向他们的最终命运。同样，在成熟神经元中，差异基因 表达和加工是结构、功能和疾病易感性的关键决定因素。然而，在这方面， 尽管这些现象已经得到了很好的证实，但一项深入而广泛的分析--涉及全基因组，神经 系统范围的数据-不适用于任何生物体。理想情况下，人们想知道，在所有神经元类型中， 以及所有的发育阶段，基因组是如何被转录和加工成有功能的RNA的。 对神经系统内差异基因表达的详细而完整的了解将有助于 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，不同性别的基因表达差异，是神经元性别差异的遗传基础。 二态性可以被阐明。梭线虫神经元基因表达图谱和网络（CeNGEN）项目 是一个多实验室联盟，目标是了解C.线虫的神经系统 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 分化和获得性二型的每一种神经元类型的C。线虫的神经系统， 这些目的：目的1）建立和分析每个神经元类型在每个阶段的基因表达图谱， 发育谱系目的2）建立一个跨性别的基因表达图谱， 性别共享神经元的基因表达，以及性别特异性神经元的基因表达。目标3）描述 所有基因和所有神经元类型的剪接模式，并使用这些信息来识别所有的 差异可变剪接目标4）生成并向科学家分发分析工具和数据 社区CeNGEN代表了神经遗传学的一个典型进展，并提供了一个独特的机会， 阐明神经元特异性基因表达的全局控制， 并拼接成最终的神经元线路和功能。CeNGEN还将作为未来研究的资源 in C. elegans神经科学，并将提供一个框架，解决全球差异基因表达， 更复杂的神经系统，目前还不适合这种全面的方法。