DIFFERENTIATION AND MORPHOGENESIS OF EXTRAEMBRYONIC MESODERM

胚外中胚层的分化和形态发生

• 批准号: 6108552
• 负责人: ROGER A. PEDERSEN
• 金额: $ 18.05万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-02-01 至 2000-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6108552
• 关键词: alleles; cell differentiation; cell type; developmental genetics; early embryonic stage; ectoderm; embryo implantation; embryonic stem cell; fibroblast growth factor; gene expression; genetic markers; growth factor receptors; human tissue; laboratory mouse; mesoderm; messenger RNA; parthenogenesis; pluripotent stem cells; transcription factor

Early development of mammalian embryos generates the extraembryonic cell lineages that provide nutritional and physical environments essential for embryonic survival. Project VI focuses on the development of extraembryonic mesoderm, one of three extraembryonic tissues formed during the peri-implantation period. Unlike trophoblast and extraembryonic endoderm lineages, which differentiate as single cell layers before implantation, extraembryonic mesoderm forms during gastrulation. Gastrulation is a complex morphogenetic process involving epithelial-mesenchymal transformation and cell migration, which transforms the epiblast layer into mesoderm, endoderm and ectoderm. Previous results of this Project strongly implicated extraembryonic mesoderm in the peri-implantation death of parthenogenetic embryos, owing to a failure of chorioallantoic fusion. The present study focuses on the origin, differentiation and morphogenesis of extraembryonic mesoderm, because this product of mammalian gastrulation is poorly understood. The Project begins by analyzing the mechanisms of mesoderm induction by peptide growth factors in peri-implantation embryos and pluripotent cells (Aim 1), continues by analyzing the roles of specific transcription factors as molecular determinants of extraembryonic mesoderm differentiation (Aim 2), and then integrates these findings with analysis of determination and other morphogenetic functions during extraembryonic mesoderm development (Aim 3). The hypothesis to be tested is that inductive events in early gastrulation are sufficient to specify an extraembryonic mesoderm fate. To approach this problem, in vitro explants of the epiblast layer will be studied to assess the effects of peptide growth factors--a mouse equivalent of the amphibian animal cap assay; gain-of-function and loss-of-function genetic transformation of embryos and pluripotent embryo-derived cells will be used to assess the role of specific growth factors; and transplantation of mesoderm cells between embryos will be used to assess their state of determination. together, these studies combine the genetic strengths of the mouse embryo system with amphibian-type experimental approaches to understand the development of this essential component of the chorioallantoic placenta. The results will contribute integrally to the Program theme on implantation and will have significant human health benefits, including implications for understanding syndromes of infertility and early pregnancy loss and inefficient implantation rates of embryos generated through medically assisted conception.

哺乳动物胚胎的早期发育会产生胚外细胞 为营养和物理环境提供必不可少的营养和物理环境的谱系 胚胎生存。 VI项目的重点是 胚外中胚层，形成的三个外胚术之一 在植入周期期间。 与滋养细胞不同 胚外内胚层谱系，与单个细胞区分开 植入前的层，胚外中胚层形式 胃。 胃胃是一个复杂的形态发生过程，涉及 上皮间质转化和细胞迁移，这 将其中海细胞层转化为中胚层，内胚层和外胚层。 该项目的先前结果强烈暗示 中胚层在孤生胚胎的植入植入术死亡中，造成 绒毛膜融合的失败。 本研究的重点是 胚外中胚层的分化和形态发生， 因为这种哺乳动物胃的产物知之甚少。 这 项目首先分析通过 植入植入胚胎和多能细胞中的肽生长因子 （AIM 1），通过分析特定转录的作用来继续 因子作为胚外中胚层的分子决定因素 分化（AIM 2），然后将这些发现与分析相结合 超胚时的确定和其他形态发生功能 中胚层开发（目标3）。 要检验的假设是 早期胃肠道的归纳事件足以指定 外囊中的中胚层命运。 要解决这个问题，体外 将研究培育层的外植物，以评估 肽生长因子 - 小鼠相当于两栖动物的动物帽 测定；功能障碍和功能丧失的遗传转化 胚胎和多能胚胎衍生的细胞将用于评估 特定生长因素的作用；和中胚层细胞的移植 在胚胎之间将用于评估其确定状态。 这些研究共同结合了小鼠胚胎的遗传强度 具有两栖动物型实验方法的系统，以了解 开发绒毛膜绒毛胎盘的基本组成部分。 结果将对计划主题的综合作用 植入并将具有重大的人类健康益处，包括 对理解不育症和早期综合症的影响 产生的胚胎的怀孕丧失和效率低下的植入率 通过医学辅助的概念。