Egg to Embryo: Gene Regulatory Circuitry in Development

卵子到胚胎：发育中的基因调控回路

基本信息

批准号：
8049418
负责人：
ERIC H DAVIDSON
金额：
$ 0.81万
依托单位：
CALIFORNIA INSTITUTE OF TECHNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-05-01 至 2010-09-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8049418
关键词：
Animals Biological Models Biological Process Biology Bite Cell Lineage Chickens Code Collaborations Communities Consultations DNA Sequence Development Developmental Biology Developmental Gene Developmental Process Drosophila genus Drug Delivery Systems Drug Formulations Embryo Embryonic Development Endomesoderm Figs - dietary Gene Components Gene Expression Gene Mutation Genes Genome Genomics Hereditary Disease Human Imaging technology In Situ Individual Intervention Knowledge Link Logic Maps Measurement Mediating Medical Medical Research Mesoderm Methods Modeling Morphogenesis Neural Crest Oral Organism Pathway Analysis Pattern Program Development Province Publications Publishing Regulator Genes Research Personnel Role Sea Urchins Signal Transduction Solutions Specific qualifier value Stretching Strongylocentrotus Structure Structure-Activity Relationship Students System Systems Biology Technology Transfer Time Work computerized tools developmental genetics egg functional genomics gastrulation member novel operation programs single molecule success symposium

项目摘要

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.)

这是一份延续和扩大项目项目的申请，该项目现已进入第 9 年。在这里，我们建议在解决和验证基因调控网络（GRN）发展方面取得的巨大成功的基础上，在多个方向上继续努力。 GRN 从基因组调控密码的角度为发育过程提供因果解释，其中所有物种特异性的发育过程都是最终被编程。发展中的 GRN 作为具有直接预测能力的概念性系统级逻辑图。因此，GRN 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做到这一点，这些相互作用因果驱动不同细胞区域中调节状态的进展。近年来，该项目一直负责最先进的实验解决方案发育 GRN 可用于任何发育中的动物有机体。这是海胆胚胎内中胚层区域规范的基础 GRN。最近，这项工作已经证明了这一原理：当 GRN 接近完成时，它确实可以解释所有观察到的生物功能。我们现在打算利用我们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所面临的挑战无法访问，或者甚至无法定义。目前的海胆胚胎GRN涉及胚胎的一半，最终形成肠道、成骨细胞谱系和非成骨中胚层，从最早的合子基因组活动（卵裂开始时）到原肠胚形成之前。口腔和体外外胚层 GRN 的研究也已开始。我们打算以不同质量的方式扩展这个 GRN，如果成功的话，这将代表着根本性的进步。在 DAVIDSON 组件中，GRN 将扩展为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表达（续）