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: 10442683
• 负责人: Deirdre C Lyons
• 金额: $ 38.7万
• 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/10442683
• 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; Embryonic Organizers; Evolution; Exhibits; Genes; Health; Human; Knowledge; Lead; Mission; Modeling; Molecular; Morphogenesis; Morphology; Nature; Nematoda; Network-based; Organism; Pathway Analysis; Pattern; Phenotype; Physiology; Research; Resolution; Snails; Stereotyping; Structure; United States National Institutes of Health; Vertebrates; ascidian; cell fate specification; cell type; comparative; gastrulation; gene regulatory network; innovation; insight; member; model building; novel; programs; tool

Project Summary: 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.

项目摘要： 细胞是所有生物结构和现象的基本单位， 新的表型和生理学最终是细胞特征变化的结果， 尤其是细胞命运的指定。在已建立的模型中充分理解细胞命运规范 系统，并且可以通过构建基因调控网络（GRNs）来描述和建模。是 基因调控网络是如何维持与修改它们的布线， 通过建立和破坏基因之间的联系来进化。其中一个障碍， 在这一领域取得的进展是缺乏后口动物以外的复杂GRN （棘皮动物、脊椎动物、海鞘）和蜕皮动物（线虫和节肢动物）。不像 这两个研究得很好的分支，螺旋藻/Lophotrochozoa尚未用于GRN 分析，尽管这一单系群包括约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。斯皮拉利亚的许多成员开始 一个共同的发展，共享一个高度定型的螺旋状分裂模式的平面图 和同源细胞谱系。在这些物种之间，细胞谱系可以在 在数亿年的进化过程中，然而螺旋藻胚胎 最终通过形态发生转变成各种各样的成体 布局没有其他地方可以在单个细胞水平上进行系统的比较， 因此，spiralians为比较发育生物学提供了一个独特的机会， 形态学水平、分子机制和同源细胞谱系。这项建议 他认为，拖鞋蜗牛Crepidula准备为GRN做出重大贡献， 在Spiralians中建立了第一个发育中的GRN。我们勾勒出一个 为每种细胞类型构建全面发育基因调控网络的策略 在Crepidula本研究将明确：1）控制形成的分子机制 （2）GRN控制 原肠胚形成在更广泛的动物中研究细胞命运的规范和形态发生将 提供了新的洞察方式GRN的运作，并将提供一个有用的比较，为其他 模型系统