DEVELOPMENTAL BIOLOGY OF THE IMPLANTING MAMMALIAN EMBRYO

这是一项研究种植体围手术期发育的新建议。 哺乳动物胚胎，特别强调形态发生事件 对植入和成功怀孕至关重要。该计划的目的是 该计划由六个项目组成，目的是研究 通过定义它们的表达和作用对植入是必不可少的 处于正常和异常植入围产期发育的产品，因此 对复杂相互作用的机制有一个基本的了解 在胚胎和子宫之间，这是胚胎存活和 生长发育和维持早孕。这些问题将是 用最先进的形态、免疫学、细胞学和 揭示基因表达本质的分子技术至关重要 用于围着床期小鼠和人类的发育使用几种不同的、 而是相辅相成的方法。第一个项目研究分布 两类细胞表面--细胞外基质黏附的作用 胚胎和细胞中的分子、整合素和细胞表面蛋白多糖 文化典范。第二个项目确定并描述了 参与侵袭过程的蛋白水解酶的发育调节 由人类滋养层细胞。第三个项目确定并描述了 生长因子及其受体在围着床期小鼠中的表达 胚胎。第四个项目分析了成长的表现和作用 与信号有关的因子及其受体和原癌基因 正常人胎盘和葡萄胎中的转导 (雄激素)。第五个项目考察了周边地区的发展。 植入隐性致死突变体，并表征了 小鼠第2、6、7、11或17号染色体以确定基因的同一性 受这些条件的影响。第六个项目分析了遗传基础 小鼠孤雌生殖和雄激素的发育失败。 行政核心将提供组织活动，以加强 调查人员之间的互动。抗体核心将是 负责产生针对由 调查人员。形态/原位定位核心将是 负责进行光学和电子显微镜组织学研究， 信使RNA的免疫组织化学和原位定位 核糖核酸的杂交。转基因/干细胞核心将负责 用于生产转基因小鼠系，并进行靶向基因 胚胎干细胞中同源重组的突变。重点放在 小鼠和人类滋养层细胞发育的结合将加强 这些研究得出的结论的概括性。这个比较性 方法应使新概念应用于临床成为可能 问题，如产前诊断、检测和治疗 滋养细胞肿瘤和不孕症的治疗。

This is a new proposal to study the peri-implantation development of the mammalian embryo, with particular emphasis on the morphogenetic events that are critical for implantation and successful pregnancy. The purpose of the program, which consists of six projects, is to study genes that are essential for implantation by defining their expression and role of their products in normal and abnormal peri-implantation development, and thus, to achieve a basic understanding of the mechanisms of the complex interactions between the embryo and uterus that are necessary for embryonic survival and growth and the maintenance of early pregnancy. These problems will be studied with state-of-the-art morphological, immunological, cellular and molecular technologies to reveal the nature of gene expression essential for peri-implantation mouse and human development using several distinct, but complementary, approaches. The first project studies the distribution and function of two classes of cell surface-extracellular matrix adhesion molecules, integrins and cell surface proteoglycans in embryos and cell culture models. The second project identifies and characterizes the developmental regulation of proteases involved in the process of invasion by human trophoblast. The third project identifies and characterizes growth factors and receptors that are expressed in peri-implantation mouse embryos. The fourth project analyzes the expression and role of growth factors, their receptors and proto-oncogenes involved in signal transduction in the normal human placenta and the hydatidiform mole (androgenote). The fifth project examines the development of peri- implantation recessive lethal mutants, and characterizes monosomies for mouse chromosomes 2, 6, 7, 11, or 17 to determine the identity of genes affected by these conditions. The sixth project analyzes the genetic basis for the developmental failure of mouse parthenogenotes and androgenotes. The administrative core will provide organizational activities to enhance the interaction between investigators. The antibody core will be responsible for generating antibodies against antigens purified by the investigators. The morphology/in situ localization core will be responsible for conducting light and electron microscopic histology, immunohistochemistry and localization of messenger RNA by in situ hybridization of mRNA. The transgenesis/stem cell core will be responsible for producing transgenic lines of mice, and for carrying out targeted gene mutation by homologous recombination in embryonic stem cells. The focus on a combination of mouse and human trophoblast development will strengthen the generality of the conclusions from these studies. This comparative approach should make possible the application of new concepts to clinical problems, such as prenatal diagnosis, detection and treatment of trophoblast neoplasia, and treatment of infertility.