Global Genomic Regulatory Code for the gastrula stage sea urchin embryo

这是该计划项目的主要组成部分。它的总体目标是通过直接 实验测定，海胆胚胎基因调控网络（GRN），以包括 口腔和反口腔外胚层、中胚层和内胚层区域的特化和分化，直到 原肠胚晚期这意味着除了顶端神经源性区域（暂时）外， 除了避免与其他实验室冗余），除了一些发展领域外， 如果在胚胎发生的后期才出现特定的胚胎，则整个胚胎将被包括在GRN中。这 该项目将首次在动物胚胎发育的任何例子中产生一个系统级模型， 胚胎设计的全球基因组调控计划。它将解释建立 空间管理状态，定义了它的大部分领土，并最终用于驱动差异化。作为 目前的海胆胚胎内中胚层GRN（仅延伸到发病时）结果显示， 的利益，科学知识的发展，可以有信心地预期，如果 本提案的主要目标可以满足，如下：（1）GRN模型可以并将通过 直接突变顺式调控分析在其关键节点，该模型因此是一个坚实的，预测性， 这是一种特异性的基因组调控系统的指示，该系统是所有胚胎发育的基础。(2)的GRN 将提供一个胚胎规格的生物学因果解释，并在全球范围内， 胚胎的设计：它将回答为什么事情会这样发展。(3)GRN将提供 比较证据需要辨别最深嵌入的子电路或核心的哺乳动物 内胚层、中胚层和可能的外胚层发育的基因组调控系统。新系统 水平的技术，仪器和增强的吞吐量方法的过程中，已经在 一方面使这个雄心勃勃的目标可行的建议，其广泛的计算基础， 由刚刚更新的NIGMS的补充赠款支持。的这一构成部分 计划项目是其他组成部分成功的基础：这些组成部分包括 GRN下游，包括形态发生的功能（组件II）;其延伸到4D 胚胎模型（组件III）;此外，将GRN分析概念转移到脊椎动物 开发规范系统（组件IV）。

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).