GLOBAL GENE REGULATORY NETWORKS FOR SPECIFIC CELL TYPES OF THE SEA URCHIN EMBRYO

海胆胚胎特定细胞类型的全球基因调控网络

• 批准号: 8288724
• 负责人: ERIC H DAVIDSON
• 金额: $ 58.13万
• 依托单位: CALIFORNIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-30 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8288724
• 关键词: Adult; Animals; Bioinformatics; Biological Models; Biological Process; Cell Lineage; Cell physiology; Cells; Cellular biology; Clinical; Code; Complementary DNA; Complex; Conserved Sequence; Development; Developmental Gene; Disease; Effector Cell; Embryo; Endoderm; Endoderm Cell; Excision; Fluorochrome; Gene Expression; Gene Expression Profile; Genes; Genomics; Immune; Instruction; Intergenic Sequence; Knock-in Mouse; Knowledge; Learning; Life; Link; Measurement; Mediating; Mesoderm; Methods; Morphogenesis; Natural Immunity; Oral; Pattern Formation; Physiological; Population; Primitive foregut structure; Problem Solving; Procedures; Process; Proteins; Proxen; Recovery; Regulator Genes; Research; Sea Urchins; Sequence Analysis; Signaling Molecule; Site; Solid; Solutions; Staging; Structure; System; Technology; Time; To specify; Validation; Work; abstracting; blastomere structure; cell type; egg; embryo cell; gastrulation; genome sequencing; interest; network models; research study; success; transcription factor

GLOBAL GENE REGULATORY NETWORKS FOR SPECIFIC CELL TYPES OF THE SEA URCHIN EMBRYO ABSTRACT All developmental, morphogenetic, and differentiation functions of animal cells are executed by large, specifically deployed batteries and cassettes of downstream protein coding genes. A major success of bioscience in recent years has been system level elucidation of the upstream gene regulatory networks (GRNs) that control pattern formation and determine development of the body plan. GRNs consist of genes encoding transcription factors and signaling molecules, plus the transcriptional linkages among these genes, and they determine the regulatory state of every cell at every point in developmental time. Therefore they include the control inputs into all the downstream genes that do the work of the cell. But an enormously important gap in understanding now separates the upstream GRNs that we are beginning to learn about from the downstream effectors of cell function: What is the actual control circuitry that determines the deployment of these downstream genes? How, exactly, are GRNs causally connected to cellular functions of differentiation and morphogenesis? In principle, given knowledge of the upstream GRN and various newly available technology, this gap can be closed, and the problem solved at a system level, and this is the particular object of the present proposal. We will choose three cell types of the developing sea urchin embryo, each of general interest. Knowledge of the upstream GRNs of this embryo is more advanced than for any other system. The target cell types are the immune cells of the embryo, where the downstream effector genes encode a great variety of innate immunity proteins; gastrulating endoderm cells, where the downstream genes mediate gastrular invagination; and the totipotent set-aside cells of the embryonic coelomic pouches that in larval stage produce the adult body plan, where the downstream effector cells include those that maintain totipotency. Innate immunity, gastrular invagination, and totipotent cell lineages are all pan-bilaterian features. The approach, briefly, will be isolation of each cell type using specific regulatory gene expression and FACS; deep transcriptome sequencing; bioinformatic prediction; and validation of causal regulatory connections to specifically expressed genes by high throughput cis- regulatory analysis. This project will provide the first global upstream-downstream GRN for any developing system. It will inform as to basic principles by which downstream gene cassettes are organized. It will also serve as a technological demonstration project for similar approaches to mammalian systems.

针对海洋特定细胞类型的全球基因调节网络 顽固的胚胎 抽象的 动物细胞的所有发育，形态发生和分化功能均由大型执行 专门部署了下游蛋白质编码基因的电池和盒式盒。一个主要成功 近年来，生物科学一直是上游基因调节网络的系统水平 （GRN）控制模式形成并确定身体计划的发展。 GRNS由基因组成 编码转录因子和信号分子，以及其中的转录联系 基因，它们在发育时间的每个点都确定了每个细胞的调节状态。所以 它们包括对控制细胞工作的所有下游基因的控制输入。但是一个巨大的 理解的重要差距现在将我们开始学习的上游grn分开 从单元函数的下游效应子中：什么是确定的实际控制电路 这些下游基因的部署？ GRNS的因果关系如何与细胞功能联系在一起 分化和形态发生？原则上，鉴于上游GRN和各种知识 新近可用的技术，该差距可以封闭，并且问题在系统级别解决，这就是 本提案的特定对象。我们将选择三种开发海胆的细胞类型 胚胎，每一个普遍兴趣。对此胚胎上游grn的了解比 对于任何其他系统。靶细胞类型是胚胎的免疫细胞，下游 效应基因编码各种先天免疫蛋白；胃内胚层细胞，其中 下游基因介导了胃部内陷；和胚胎的固定细胞 Coelomic小袋在幼虫阶段产生成人身体计划，下游效应细胞 包括那些维持动力的。先天免疫力，胃部内陷和全能细胞谱系 都是泛 - 甲腔的特征。简而言之，该方法将使用特定 调节基因表达和FACS；深度转录组测序；生物信息学预测；和 通过高吞吐量顺式验证与特定表达基因的因果调节连接的验证 监管分析。该项目将为任何开发 系统。它将告知下游基因盒的基本原理。它也会 作为一个技术演示项目，用于针对哺乳动物系统的类似方法。