Egg to Embryo: Gene Regulatory Circuitry in Development

这是一份申请，申请延续和扩大一个已进入第9个年头的项目。在这里，我们建议在许多方向上建立我们在解决和验证基因调控网络（GRN）的发展方面取得的巨大成功。grn从基因组调控代码的角度为发育过程提供了因果解释，其中所有物种特异性发育过程最终都被编程。一个发展中的GRN作为一个概念性的、系统级的逻辑图，具有直接的预测能力。因此，grn在具有调控意义的功能基因组DNA序列与胚胎发生和体表形成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，这些相互作用导致了不同细胞区域中调控状态的进展。近年来，该计划一直负责为任何正在发育的动物有机体提供最先进的发育GRN的实验解决方案。这是GRN的基础

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.)