Global Genomic Regulatory Code for the gastrula stage sea urchin embryo

原肠胚阶段海胆胚胎的全球基因组监管代码

• 批准号: 8092699
• 负责人: ERIC H DAVIDSON
• 金额: $ 68.02万
• 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: 2010-06-01 至 2014-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8092699
• 关键词: Animals; Apical; Biological; Biological Process; Biology; Cells; Cellular biology; Code; Development; Developmental Biology; Developmental Gene; Ectoderm; Embryo; Embryonic Development; Endoderm; Endomesoderm; Engineering; Event; Gastrocoele; Gastrula; Gene Transfer; Genes; Genome; Genomics; Grant; Hand; Hindgut; Instruction; Knowledge; Lead; Link; Mesoderm; Mesoderm Cell; Methodology; Methods; Midgut; Modeling; Molecular; Morphogenesis; National Institute of General Medical Sciences; Neural Crest; Oral; Organism; Pathway Analysis; Phase; Plant Roots; Play; Primitive foregut structure; Procedures; Process; Proteins; Regulator Genes; Sampling; Sea Urchins; Signal Transduction; Solid; Specific qualifier value; Staging; Structure; System; Technology; Technology Transfer; Time; Validation; Work; base; c new; cell type; comparative; design; follow-up; gastrulation; instrumentation; meetings; network models; operation; oral ectoderm; programs; success; theories; transcription factor

This is the lead Component of the Program Project. Its overall objective is to expand understanding, by direct experimental determination, of the sea urchin embryo gene regulatory network (GRN) so as to encompass specification and differentiation of oral and aboral ectoderm, mesoderm, and endoderm territories up until late gastrula period. This means that with the exception of the apical neurogenic territory (provisionally excepted to avoid redundancy with other labs), and with the exception of a few developmental territorial specifications which occur only late in embryogenesis, the entire embryo will be included in the GRN. This project will yield, for the first time in any example of animal embryonic development, a system-level model of the global genomic regulatory program for the design of the embryo. It will explain the establishment of the spatial regulatory states that define most of its territories, and that ultimately serve to drive differentiation. As shown by current results with the sea urchin embryo endomesodermal GRN (which extends only to the onset of gastrulation) the benefits to scientific knowledge of development that can confidently be expected if the main objective of this proposal can be met, are as follows: (1) The GRN model can and will be validated by direct mutational cis-regulatory analysis at its key nodes and the model is therefore a solid, predictive, and specific, indication of the genomic regulatory system that underlies all embryonic development. (2) The GRN will provide a causal explanation of the biology of embryonic specification, and on a global scale, of the design of the embryo: it will answer why events proceed as they do. (3) The GRN will provide the comparative evidence required to discern the most deeply embedded subcircuits or kernels of mammalian genomic regulatory systems for endoderm, mesoderm, and perhaps ectoderm development. New system level technologies, instrumentation, and enhanced throughput methods of procedure which are already in hand make the ambitious objective of this proposal feasible, and its extensive computational underpinnings are supported by a complementary grant from the NIGMS which has just been renewed. This Component of the Program Project is basic to the success of the other Components: these consist of extensions of the GRN downstream, to encompass the functions of morphogenesis (Component II); its extension into a 4D model of the embryo (Component III); and in addition, transfer of GRN analysis concepts to a vertebrate developmental specification system (Component IV).

这是程序项目的主要组成部分。它的总体目标是通过直接扩展理解 海胆胚胎基因调节网络（GRN）的实验确定，以包含 口头和原住民的规格和差异化，中胚层以及内胚层领土直到 胃晚期。这意味着除了根尖神经源区域（临时 除了少数发展领土外，避免对其他实验室的冗余）除外。 仅在胚胎发生中发生的规格，整个胚胎将包含在GRN中。这 在任何动物胚胎开发的例子中，项目都将首次产生。 胚胎设计的全球基因组调节计划。它将解释建立 空间监管规定定义其大多数领土，并最终有助于差异化。作为 由海胆胚胎内胚层gRN当前结果显示（仅延伸至发作 胃术）对发展科学知识的好处，如果 可以满足该提案的主要目标，如下：（1）GRN模型可以并且将通过 因此，直接的突变顺式调节性分析在其关键节点上，该模型是一个固体，预测性和 基因组调节系统的具体指示，该系统是所有胚胎发育的基础。 （2）GRN 将提供有关胚胎规范生物学的因果解释，并在全球范围内对 胚胎的设计：它将回答为什么事件像他们一样进行。 （3）GRN将提供 辨别哺乳动物最深层嵌入的亚电路或核所需的比较证据 内胚层，中胚层以及外胚层发育的基因组调节系统。新系统 水平技术，仪器和增强的过程的吞吐量方法已经存在 手使该提案可行的雄心勃勃的目标及其广泛的计算基础 由刚刚续签的Nigms的补充赠款支持。这个组成部分 该计划项目是其他组件成功的基础 下游的GRN，以包含形态发生的功能（成分II）；它扩展到4D 胚胎的模型（组件III）；此外，将GRN分析概念转移到脊椎动物 发展规范系统（组件IV）。