A Morphology and Gene Expression Atlas for Drosophila Embryogenesis

果蝇胚胎发生的形态学和基因表达图谱

• 批准号: 8292105
• 负责人: David W. Knowles
• 金额: $ 49.43万
• 依托单位: UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-01 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8292105
• 关键词: Anatomy; Animals; Apoptotic; Atlases; Blastoderm; Caenorhabditis elegans; Cell Nucleus; Cell membrane; Cells; Characteristics; Classification; Communities; Complex; Computer Simulation; Data; Data Set; Databases; Development; Drosophila genus; Drosophila melanogaster; Electronics; Embryo; Embryonic Development; Event; Gene Expression; Gene Expression Profile; Genes; Goals; Hour; Image; Image Analysis; Imagery; Lead; Learning; Life; Light; Link; Location; Maps; Methods; Mitotic; Molecular; Morphology; Motion; Movement; Nuclear; Ontology; Optics; Organ; Pattern; Positioning Attribute; Proteins; Regulator Genes; Regulatory Pathway; Research; Research Personnel; Resolution; Resources; Shapes; Staging; Staining method; Stains; Structure; Study models; Systems Biology; Time; Tissues; Work; base; biological research; cell type; cellular imaging; computational atlas; computerized tools; developmental genetics; fluorescence imaging; fly; imaging Segmentation; mRNA Expression; protein expression; public health relevance; tool

DESCRIPTION (provided by applicant): Animals comprise complex, dynamic, three dimensional arrays of cells which differ from each other in histological type, shape, size, location, and other characteristics. These differences-and the resulting higher order tissue/morphological structures that they in turn generate-ultimately derive from intricate patterns of gene expression that develop during embryogenesis. A deep understanding of these complex, quantitative changes in morphology and gene expression will require a detailed, precise description of morphological and expression dynamics at cellular resolution. We propose to create a quantitative, cellular resolution map of gene expression and morphology for all of embryo development for one of the most studied model animals: Drosophila melanogaster. This goal will extend our previous work which has established a suite of live and fixed embryo imaging and image analysis methods that have provided the first quantitative description of gene expression and morphology at cellular resolution of an intact early stage Drosophila embryo and have revealed previously unknown features about the biology of this system. The early stage blastoderm embryos analyzed in these initial studies, however, have a relatively simple structure that is comprised of a single layer of some 6000 cells surrounding a yolk. After the blastoderm stage-over the course of ten hours-three mitotic cycles, large cell motions and complex patterns of differentiation lead to the formation of over 70 cell types and all major larval organs. To accurately capture this great increase in complexity, we propose to make major improvements in our imaging and image segmentation strategies, establish learning based classification methods to assign cells to specific cell types and tissues, and develop more sophisticated visualization tools to allow exploration of the data. Our preliminary data show that it is possible to image all cells throughout Drosophila embryogenesis and suggest a way to create a morphological framework on which to quantitate gene expression. The availability of a qualitative cellular resolution atlas has been a boon to the analysis of C elegans over the last twenty years. Our proposed more sophisticated, quantitative, computational model of Drosophila embryogenesis will inevitably be at least as significant resources to the fly community and will open the way for data based, computational modeling of tissue formation and the associated gene regulatory networks. PUBLIC HEALTH RELEVANCE: Our project to create a quantitative, cellular resolution map of gene expression and morphology of embryogenesis will produce tools which will significantly advance basic biological research. Converting an animal embryo into a computational atlas of its body plan, cell positions, cell fate and tissue locations, along with a cellular resolution map of gene expression, will provide a portable anatomical and expression atlas that can be dissected and observed by any researcher. This electronic embryonic atlas, will not only be an invaluable educational tool, but will allow cellular resolution anatomical analyses of anatomy in 3D, will shed light on the regulatory pathways, allow new types of computational systems biology and it will integrate anatomy with molecular developmental genetics.

描述（由申请人提供）：动物包含复杂的、动态的、三维的细胞阵列，这些细胞的组织学类型、形状、大小、位置和其他特征彼此不同。这些差异以及由此产生的更高阶组织/形态结构最终源自胚胎发生过程中形成的复杂的基因表达模式。要深入了解形态学和基因表达的这些复杂的定量变化，需要在细胞分辨率下对形态学和表达动态进行详细、精确的描述。我们建议为研究最多的模型动物之一：黑腹果蝇的所有胚胎发育创建定量的、细胞分辨率的基因表达和形态学图谱。这一目标将扩展我们之前的工作，我们已经建立了一套活体和固定胚胎成像和图像分析方法，这些方法首次以细胞分辨率定量描述了完整的早期果蝇胚胎的基因表达和形态，并揭示了该系统的生物学特征。然而，这些初步研究中分析的早期胚盘胚胎具有相对简单的结构，由围绕卵黄的单层约 6000 个细胞组成。在胚盘阶段（历时十个小时）三个有丝分裂周期之后，大的细胞运动和复杂的分化模式导致 70 多种细胞类型和所有主要幼虫器官的形成。为了准确捕捉这种复杂性的巨大增加，我们建议对成像和图像分割策略进行重大改进，建立基于学习的分类方法将细胞分配给特定的细胞类型和组织，并开发更复杂的可视化工具以允许探索数据。我们的初步数据表明，可以对果蝇胚胎发生过程中的所有细胞进行成像，并提出了一种创建形态学框架来定量基因表达的方法。在过去的二十年中，定性细胞分辨率图谱的可用性对于线虫的分析来说是一个福音。我们提出的果蝇胚胎发生的更复杂、定量的计算模型将不可避免地成为果蝇界至少同样重要的资源，并将为基于数据的组织形成和相关基因调控网络的计算模型开辟道路。 公共健康相关性：我们的项目旨在创建胚胎发生的基因表达和形态的定量细胞分辨率图，这将产生将显着推进基础生物学研究的工具。将动物胚胎转化为包含其身体结构、细胞位置、细胞命运和组织位置的计算图谱，以及基因表达的细胞分辨率图，将提供任何研究人员都可以解剖和观察的便携式解剖和表达图谱。该电子胚胎图谱不仅是一种宝贵的教育工具，而且将允许对 3D 解剖学进行细胞分辨率解剖分析，将阐明调控途径，允许新型计算系统生物学，并将解剖学与分子发育遗传学相结合。