Global Genomic Regulatory Code for the gastrula stage sea urchin embryo

这是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 海胆胚胎基因调控网络(GRN)的实验测定 口腔和败育的外胚层、中胚层和内胚层直到 原肠胚晚期。这意味着除了顶端的神经源性区域(暂时的 以避免与其他实验室的冗余)，以及除少数开发地区外 只有在胚胎发育后期才出现的规格，整个胚胎都将包括在GRN中。这 该项目将在任何动物胚胎发育的例子中首次产生一个系统级的模型 胚胎设计的全球基因组调控计划。它将解释如何建立 空间监管州定义了它的大部分领土，并最终推动了差异化。AS 海胆胚胎内胚层GRN(仅延伸到发病)的当前结果显示 原肠发育的科学知识的好处可以自信地预期，如果 这项建议的主要目标可以达到，如下：(1)GRN模型可以并将通过以下方式进行验证 在其关键节点进行直接突变顺式分析，因此该模型是可靠的、可预测的和 所有胚胎发育所依据的基因组调控系统的具体指示。(2)GRN 将提供胚胎生物学规范的因果解释，并在全球范围内解释 胚胎的设计：它将回答为什么事情会这样进行。(3)GRN将提供 辨别哺乳动物最深层嵌入的亚回路或核心所需的比较证据 内胚层、中胚层和外胚层发育的基因组调控系统。新系统 已经在使用的程序的水平技术、工具和增强的吞吐量方法 Hand使这项建议的宏伟目标及其广泛的计算基础变得可行 由刚刚续签的NIGMS提供的补充赠款支持。此组件 计划项目是其他组件成功的基础：这些组件包括 GRN下游，包括形态发生功能(成分II)；其延伸为4D 胚胎模型(组成三)；此外，将GRN分析概念转移到脊椎动物 发展规格体系(构成部分四)。

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).