Building a gene regulatory network-based model for cell fate specification and morphogenesis using a new mollusc model.

使用新的软体动物模型构建基于基因调控网络的细胞命运规范和形态发生模型。

• 批准号: 10478389
• 负责人: Deirdre C Lyons
• 金额: $ 4.7万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-15 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10478389
• 关键词: Adult; Animals; Area; Arthropods; Behavior; Biological; Biological Models; Biology; Cell Lineage; Cell model; Cells; Characteristics; Development; Developmental Biology; Developmental Gene; Echinodermata; Embryo; Embryology; Embryonic Organizers; Evolution; Genes; Genetic; Health; Knowledge; MAP Kinase Gene; Maps; Microinjections; Mission; Modeling; Molecular; Morphogenesis; Morphology; Nature; Nematoda; Network-based; Organism; Pathway Analysis; Pattern; Phenotype; Physiology; Regulation; Research; Resolution; Role; Signal Transduction; Snails; Stereotyping; Structure; United States National Institutes of Health; Vertebrates; ascidian; cell fate specification; cell type; comparative; gastrulation; gene regulatory network; insight; member; model building; novel; parent grant; tool

PARENT GRANT ABSTRACT Cells are the fundamental units of all biological structures and phenomena—the evolution of novel phenotypes and physiologies is ultimately the result of changes in cellular characteristics, especially cell fate specification. Cell fate specification is well understood in established model systems, and can be described and modelled by building gene regulatory networks (GRNs). It is not well-understood how gene regulatory networks maintain vs modify their wiring over evolution, by making and breaking connections between genes. One of the impediments to making progress in this area is the lack of sophisticated GRNs outside of deuterostomes (echinoderms, vertebrates, ascidians) and ecdysozoans (nematodes and arthropods). Unlike these two well-studied clades, the Spiralia/Lophotrochozoa has not been used for GRN analysis, despite the fact that this monophyletic group includes ~40% of extant animal body plans, including familiar taxa like annelids and molluscs. Many members of the Spiralia begin development with a common ground plan sharing a highly stereotyped pattern of spiral cleavage and homologous cell lineages. Between these species, cell lineages can be homologized at single-cell resolution across hundreds of millions of years of evolution. Yet Spiralian embryos ultimately are transformed through morphogenesis into a vast array of diverse adult body plans. Nowhere else can one undertake systematic comparisons at a single-cell level between body plans; thus spiralians offer a unique opportunity for comparative developmental biology at the level of morphology, molecular mechanisms, and homologous cell lineages. This proposal argues that the slipper snail Crepidula is poised to make significant contributions to GRN biology by being used to build the first developmental GRN among Spiralians. We outline a strategy to build a comprehensive developmental gene regulatory network for every cell type in Crepidula. This research will define: 1) the molecular mechanisms controlling the formation and function of the Crepidula embryonic organizer and 2) the GRN controlling gastrulation. Studying cell fate specification and morphogenesis in a wider range of animals will provide fresh insight into the ways GRNs operate, and will provide a useful comparison for other model systems.

家长补助金摘要 细胞是所有生物结构和现象的基本单位——生物的进化 新的表型和生理学最终是细胞特征变化的结果， 特别是细胞命运规范。细胞命运规范在已建立的模型中得到很好的理解 系统，并且可以通过构建基因调控网络（GRN）来描述和建模。这是 不太了解基因调控网络如何维持或修改其接线 进化，通过建立和打破基因之间的联系。障碍之一 在这一领域取得进展的原因是后口动物之外缺乏复杂的 GRN （棘皮动物、脊椎动物、海鞘动物）和蜕皮动物（线虫和节肢动物）。不像 这两个经过充分研究的进化枝，螺旋虫/冠轮虫尚未用于 GRN 分析，尽管事实上这个单系群包括约 40% 的现存动物体 计划，包括熟悉的类群，如环节动物和软体动物。许多螺旋体成员开始 具有共同平面的开发，具有高度定型的螺旋分裂模式 和同源细胞谱系。在这些物种之间，细胞谱系可以在以下位置同源： 跨越数亿年进化的单细胞分辨率。然而螺旋胚胎 最终通过形态发生转化为各种各样的成人身体计划。 没有其他地方可以在单细胞水平上对身体之间进行系统比较。 计划；因此，螺旋虫为比较发育生物学提供了独特的机会 形态学、分子机制和同源细胞谱系的水平。这个提议 认为拖鞋蜗牛 Crepidula 有望为 GRN 做出重大贡献 生物学，被用来构建螺旋人中的第一个发育 GRN。我们概述了一个 为每种细胞类型建立全面的发育基因调控网络的策略 苋菜属。这项研究将定义：1）控制形成和形成的分子机制。 Crepidula 胚胎组织者的功能和 2) GRN 控制原肠胚形成。学习中 更广泛动物的细胞命运规范和形态发生将提供新的见解 深入了解 GRN 的运作方式，并将为其他模型系统提供有用的比较。