DEVELOPMENTAL BIOLOGY OF THE IMPLANTING MAMMALIAN EMBRYO

哺乳动物胚胎植入的发育生物学

基本信息

批准号：
6151140
负责人：
Roger Arnold Pedersen
金额：
$ 112.62万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
1991
资助国家：
美国
起止时间：
1991-02-01 至 2002-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6151140
关键词：
developmental genetics early embryonic stage embryo implantation gene expression

项目摘要

This Program Project emphasizes the molecular and cellular events of mammalian implantation and placental formation, an essential but little- studied process in early reproduction that has great significance for human health. The purpose of the Program is to define the role of genes that are essential for implantation and thus to achieve a basic understanding of the interactions between the embryo and uterus that establish pregnancy. The Program focuses on the peri-implantation development of the three tissue lineages that mediate implantation and develop into the placenta and fetal membranes, namely, trophoblast, extraembryonic endoderm, and extraembryonic mesoderm. Four projects examine the roles of individual membranes of several superfamilies of genes whose products are implicated in controlling peri-implantation development and implantation. These include the extracellular matrix receptors, or integrins, proteases and their inhibitors, peptide growth factors and their receptors, and HLH and other transcription factors. Project I examines the role of integrin receptors for extracellular matrix in peri-implantation development of trophoblast and primitive endoderm; Project II analyzes the roles of helix-loop-helix transcription factors in regulating human trophoblast invasion; Project III studies the mechanisms regulating growth, cell division and differentiation during morphogenesis of extraembryonic lineages and in the invasive process in vivo; and Project VI analyzes the differentiation and morphogenesis of extraembryonic mesoderm, especially the allantois. The Projects are supported by an Administrative Core, which provides fiscal management, and two research cores, the Morphology/Cytogenetics Core, which provides histological, in situ hybridization, confocal microscopy, and chromosomal analysis services, and the Cell Culture/Targeted Mutagenesis Core, which provides cell culture and genetic transformation services, including all the activities needed for targeted mutagenesis in mice. The proposed studies have major implications for human health problems, including syndromes of infertility and early pregnancy loss, inefficient implantation rates of embryos generated through medically assisted conception, and diseases of the trophoblast such as choriocarcinoma, hydatidiform mole and pre-eclampsia. These problems can ultimately be resolved only through mammalian studies, as undertaken in the Program, which examine the fundamental mechanisms of embryo-maternal interactions.

该程序项目强调了分子和细胞事件哺乳动物植入和胎盘形成，这是必不可少但少的在早期繁殖中研究的过程对人类健康。该程序的目的是定义基因的作用这对于植入至关重要，因此要实现基本了解胚胎和子宫之间的相互作用建立怀孕。该计划的重点是植入周期开发介导植入和的三个组织谱系发育到胎盘和胎儿膜中，即滋养细胞，胚外内胚层和胚外中胚层。四个项目检查几个超家族的单个膜的作用产物与控制植入周期有关的基因发展和植入。这些包括细胞外基质受体或整联蛋白，蛋白酶及其抑制剂，肽生长因素及其受体，HLH和其他转录因子。项目I研究了整联蛋白受体在细胞外的作用培养细胞和原始植入植入术发展的基质内胚层；项目II分析螺旋环螺旋转录的作用调节人类滋养细胞入侵的因素；项目III研究调节生长，细胞分裂和分化的机制外胚谱系的形态发生以及在侵入性过程中体内项目VI分析了分析和形态发生胚外中胚层，尤其是阿兰托瓦。项目是在提供财政管理的行政核心的支持下，和两个研究核心，形态/细胞遗传学核心，提供组织学，原位杂交，共聚焦显微镜和染色体分析服务以及细胞培养/靶向诱变核心，这提供细胞培养和遗传转化服务，包括所有小鼠靶向诱变所需的活动。提议研究对人类健康问题有重大影响，包括不育症和早期妊娠损失的综合征，效率低下通过医学辅助产生的胚胎的植入率构思和滋养细胞的疾病，例如绒毛膜癌，氢化痣和前球。这些问题最终可能是仅通过该计划中的哺乳动物研究解决，它检查了胚胎 - 伴侣相互作用的基本机制。