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

项目总结： 细胞是所有生物结构和现象的基本单位--生物进化 新的表型和生理最终是细胞特性变化的结果， 尤其是细胞命运规范。细胞命运规范在已建立的模型中得到了很好的理解 系统，并可以通过建立基因调控网络(GRN)来描述和建模。它是 还不清楚基因调控网络是如何维持和修改它们的连接的 进化，通过建立和切断基因之间的联系。阻碍之一是 在这一领域取得进展的是在后口以外缺乏复杂的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 这两个研究得很好的分支，螺旋藻/细毛虫还没有被用于GRN 分析，尽管这个单系类群包括现存动物身体的40%左右 计划，包括熟悉的分类群，如环节动物和软体动物。许多精灵的成员开始 具有共同基础计划的发展，共享高度定型的螺旋式分裂模式 以及同源的细胞谱系。在这些物种之间，细胞谱系可以在 跨越数亿年进化的单细胞分辨率。然而，螺纹族胚胎 最终通过形态发生转变成大量不同的成体 计划。没有其他地方可以在单细胞水平上进行系统的比较 身体计划；因此，螺旋虫为比较发育生物学提供了一个独特的机会 形态水平、分子机制和同源细胞谱系。这项建议 认为拖鞋蜗牛Crepidula将对GRN做出重大贡献 被用来在螺旋虫中建立第一个发育的GRN。我们勾勒出一个 为每种细胞类型建立全面的发育基因调控网络的策略 在克雷皮杜拉。这项研究将确定：1)控制形成的分子机制 和Crepidula胚胎组织者的功能以及2)GRN的控制 原肠形成。在更广泛的动物中研究细胞命运指定和形态发生将 为GRN的运作方式提供新的见解，并将为其他 模型系统。

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.