Body Plan Formation in Early Mouse Embryo

早期小鼠胚胎的身体计划形成

基本信息

批准号：
6536304
负责人：
YUSUKE MARIKAWA
金额：
$ 17.79万
依托单位：
UNIVERSITY OF HAWAII AT MANOA
依托单位国家：
美国
项目类别：
财政年份：
2001
资助国家：
美国
起止时间：
2001-05-08 至 2005-04-30
项目状态：
已结题

项目摘要

DESCRIPTION: (Scanned from the applicant's abstract) The basic architecture of animal bodies is established during early embryogenesis. Compared to other vertebrate systems, little is known about how a mammalian egg creates the basic body plan. The major goal of this study is to elucidate the molecular mechanisms responsible for cell fate determination and body axis formation in the mouse embryo. The first specific aim of this study is to identify cytoplasmic and membrane components in the egg that are involved in the formation of the inner cell mass (ICM) and the trophectoderm (TE). Formation of the ICM and TE is the first cell differentiation event in mouse development. We will use lineage-specific molecular markers to identify the differentiation of these two distinct cell types in embryos treated with various inhibitors of the cytoskeleton, membrane trafficking and cell adhesion. We will also investigate the role of egg cytoplasmic components in the ICM and TE development. For this study, we will exploit the centrifugation techniques, which have been successfully used to identify developmentally important factors in the egg of other vertebrates and chordates. The second aim is to analyze the function of localized molecules in the egg, namely Stat3 and Leptin proteins. Since both Stat3 and Leptin act as regulators of cell differentiation and growth in many systems, we hypothesize that the localized distribution of Stat3 and Leptin in the egg plays an important role in the establishment of the body plan. We will test this hypothesis by overexpressing Stat3 and Leptin in the mouse egg to disturb their normal distribution. We will also use constitutive active and dominant negative constructs of Stat3 to examine the function of the localized Stat3 in more detail. The third aim is to define the role of the Wnt/b-catenin signaling pathway in body axis formation in the embryo. Although the signaling pathway is suggested to be involved in axis formation in the mouse embryo, its mode of action is not as clear as in other vertebrate systems, specifically the frog. We will define the role of the Wnt/b-catenin signaling pathway in the mouse axis formation in more detail by introducing inhibitory constructs of the signaling pathway, and by locally activating the signaling pathway in early embryos. The studies proposed in this application should enable us to better understand the molecular mechanisms of the earliest critical events in mammalian body plan formation, and provide clues to resolve many problems associated with human birth defects as well as biomedical technology.

描述：（从申请人的摘要中扫描）的基本架构动物体是在早期胚胎发生过程中建立的。与其他相比在脊椎动物系统中，人们对哺乳动物的卵如何产生基本的物质知之甚少。身体计划。本研究的主要目标是阐明分子负责细胞命运决定和身体轴形成的机制小鼠胚胎。本研究的第一个具体目标是确定卵子中参与细胞质和膜的成分内细胞团（ICM）和滋养外胚层（TE）的形成。的形成 ICM 和 TE 是小鼠发育过程中的第一个细胞分化事件。我们将使用谱系特异性分子标记来识别用各种抑制剂处理的胚胎中的这两种不同的细胞类型细胞骨架、膜运输和细胞粘附。我们也会调查卵细胞质成分在 ICM 和 TE 发育中的作用。为了这研究中，我们将利用离心技术，该技术已被成功用于识别卵子中发育的重要因素其他脊椎动物和脊索动物。第二个目的是分析鸡蛋中的局部分子，即 Stat3 和瘦素蛋白。既然两者 Stat3 和瘦素在许多细胞中充当细胞分化和生长的调节剂系统中，我们假设 Stat3 和瘦素的局部分布鸡蛋在身体计划的建立中起着重要作用。我们将通过在小鼠卵中过度表达 Stat3 和 Leptin 来检验这一假设扰乱它们的正常分布。我们还将使用本构主动和 Stat3 的显性负构建体用于检查局部化的功能 Stat3 更详细。第三个目标是确定 Wnt/b-catenin 的作用胚胎体轴形成中的信号通路。虽然信号建议该途径参与小鼠胚胎中轴的形成，其作用方式不像其他脊椎动物系统那么清楚，特别是青蛙。我们将定义 Wnt/b-catenin 信号通路在通过引入抑制结构更详细地观察小鼠轴的形成信号通路，并通过在早期局部激活信号通路胚胎。本申请中提出的研究应该使我们能够更好地了解最早关键事件的分子机制哺乳动物身体计划的形成，并为解决许多问题提供线索与人类出生缺陷以及生物医学技术有关。