Egg to Embryo: Gene Regulatory Circuitry in Development

这是一份延续和扩大计划项目的申请，该计划项目现已进入9*年。在这里，我们建议在解决和验证用于开发的基因调控网络(GRN)方面取得的巨大成功的基础上，建立多个方向。GRN在基因组调控代码方面为发育过程提供了因果解释，其中所有物种特定的发育过程都是 最终被编程。发展性GRN是一个概念性的、系统级的逻辑地图，具有直接的预测力。因此，GRNS在具有调控意义的功能基因组DNA序列和胚胎发生和身体计划形成的生物学之间架起了桥梁。他们通过指定调控相互作用来做到这一点，这些调控相互作用在不同的细胞领域中因果地推动了监管状态的进展。近年来，该计划一直负责最先进的实验解决方案 发育中的GRN对任何发育中的动物有机体都是可用的。这是海胆胚胎内胚层区域规范所依据的GRN。最近，这项工作证明了当GRN接近完成时，它确实提供了对所有观察到的生物功能的解释。我们现在打算利用我们开发的越来越多的成功的技术方法来进行GRN分析，以应对在此之前 无法访问，或者甚至不能被定义。目前的海胆胚胎GRN大约涉及胚胎的一半，最终形成肠道、骨骼细胞谱系和非骨骼发育的中胚层，从最早的合子基因组活动(卵裂开始)到原肠形成之前。口腔和流产外胚层GRN的研究也已开始。我们打算以不同的方式扩展这一GRN，如果成功，这将代表着根本性的进步。 在Davidson组件中，GRN将扩展到包括通过基因组分析预测的所有调控基因，并观察到在内胚层区域特异表达，(续)

This is an application for continuation and broadening of a Program Project now in its 9* 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.)