Egg to Embryo: Gene Regulatory Circuitry in Development

卵子到胚胎：发育中的基因调控回路

• 批准号: 8278613
• 负责人: ERIC H DAVIDSON
• 金额: $ 164.25万
• 依托单位: CALIFORNIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-04-01 至 2014-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8278613
• 关键词: Egg; Embryo; Gene; Regulatory; Circuitry

This is an application for continuation and broadening of a Program Project now in its 9th year. Here we propose to build in many directions on the large success we have had in solving and authenticating a gene regulatory network (GRN) for development. GRNs provide causal explanations for developmental processes in the terms of the genomic regulatory code, where all species-specific developmental processes are ultimately programmed. A developmental GRN serves as a conceptual, system-level logic map, of direct predictive power. Thus GRNs bridge between functional genomic DNA sequence of regulatory significance and the biology of embryogenesis and body plan formation. They do this by specifying the regulatory interactions which causally drive the progression of regulatory states in diverse cellular territories. During recent years, this Program has been responsible for the experimental solution of the most advanced developmental GRN yet available for any developing animal organism. This is the GRN underlying the specification of the endomesodermal territories of the sea urchin embryo. Recently proof of the principle that as a GRN approaches completion it indeed provides explanation of all the observed biological functions has been obtained in this work. We now intend to capitalize on the growing suite of successful technological approaches to GRN analysis that we have developed, to confront challenges that heretofore were inaccessible, or could not even have been defined. The current sea urchin embryo GRN concerns about half of the embryo, that ultimately forming the gut, the skeletogenic cell lineages and the non-skeletogenic mesoderm, from the earliest zygotic genomic activity (at the beginning of cleavage) to just before gastrulation. A start on the oral and aboral ectodermal GRNs has also been made. We intend to expand this GRN in qualitatively distinct ways which will represent radical advances if successful. In the DAVIDSON COMPONENT the GRN will be expanded to include all regulatory genes predicted by genomic analysis, and observed to be expressed specifically in the endomesodermal territories, (cont.)

这是一个延续和扩大计划项目的申请，现在已经是第九年了。在这里，我们建议建立在许多方向上的巨大成功，我们已经在解决和验证一个基因调控网络（GRN）的发展。GRNs在基因组调控密码方面为发育过程提供了因果解释，所有物种特异性发育过程最终都是编程的。一个发展的GRN作为一个概念，系统级的逻辑地图，直接预测能力。因此，GRNs在具有调节意义的功能基因组DNA序列与胚胎发生和身体计划形成的生物学之间架起了桥梁。他们通过指定调节相互作用来实现这一点，这些相互作用因果地驱动不同细胞区域中调节状态的进展。近年来，该计划一直负责为任何发育中的动物生物体提供最先进的发育GRN的实验解决方案。这是GRN的基础， 海胆胚胎的内中胚层领土的规格。最近的证明的原则，作为一个GRN接近完成，它确实提供了所有观察到的生物功能的解释已经在这项工作中获得。我们现在打算利用我们已经开发的越来越多的成功的GRN分析技术方法来应对迄今为止无法实现的挑战，甚至无法定义。目前的海胆胚胎GRN关注约一半 从最早的合子基因组活动（在卵裂开始时）到原肠胚形成之前，胚胎的发育过程包括最终形成肠、骨骼发生细胞谱系和非骨骼发生中胚层。口腔和离口外胚层GRN也已开始。我们打算以不同的方式扩大GRN，如果成功的话，这将代表根本性的进步。 在DAVIDSON COMPONENT中，GRN将扩展到包括通过基因组分析预测的所有调控基因，并观察到在内中胚层区域特异性表达。