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).

这是该计划项目的主要组成部分。其总体目标是通过直接的方式扩大理解 实验测定海胆胚胎基因调控网络（GRN），以便涵盖 口和口外外胚层、中胚层和内胚层区域的规范和分化，直到 原肠胚晚期。这意味着除了顶端神经源性区域（暂时） 避免与其他实验室重复的情况除外），并且除了一些发展领域之外 如果规范仅在胚胎发生后期发生，则整个胚胎将包含在 GRN 中。这 该项目将在动物胚胎发育的任何例子中首次产生一个系统级模型 用于胚胎设计的全球基因组调控计划。它将解释该机构的设立 空间监管国家定义了其大部分领土，并最终有助于推动差异化。作为 目前海胆胚胎内中胚层 GRN 的结果显示（仅延伸到起始阶段） 原肠胚形成）如果 该提案可以实现的主要目标如下： (1) GRN 模型可以并且将会通过 在其关键节点进行直接突变顺式调控分析，因此该模型是可靠的、预测性的和 是所有胚胎发育基础的基因组调控系统的具体指示。 （2）GRN 将为胚胎规范的生物学以及全球范围内的胚胎规范提供因果解释 胚胎的设计：它将回答事件为什么会这样进行。 (3) GRN 将提供 辨别哺乳动物最深嵌入的子电路或内核所需的比较证据 内胚层、中胚层，或许还有外胚层发育的基因组调控系统。新系统 水平技术、仪器和增强吞吐量的程序方法已经在 手工使该提案的雄心勃勃的目标变得可行，及其广泛的计算基础 得到了 NIGMS 刚刚更新的补充赠款的支持。该组件的 该计划项目是其他组件成功的基础：这些组件包括 GRN 下游，涵盖形态发生的功能（组件 II）；将其扩展到 4D 胚胎模型（组件 III）；此外，将 GRN 分析概念转移到脊椎动物 发展规范系统（第四部分）。