DEVELOPMENTAL BIOLOGY OF THE IMPLANTING MAMMALIAN EMBRYO

这为研究胚胎着床期发育提供了新的思路。 哺乳动物胚胎，特别强调形态发生事件， 对着床和成功怀孕至关重要 的目的 该计划由六个项目组成，旨在研究 通过定义它们的表达和作用， 正常和异常围着床期发育的产品，因此， 对复杂相互作用的机制有基本的了解 胚胎和子宫之间的关系，这是胚胎生存所必需的， 生长和维持早期妊娠。 这些问题将 用最先进的形态学、免疫学、细胞学和 分子技术揭示基因表达的本质至关重要 对于围着床期小鼠和人类发育， 而是互补的方法。 第一个项目研究分布 两类细胞表面-细胞外基质粘附功能 分子、整合素和细胞表面蛋白多糖 文化模式 第二个项目确定并描述了 参与入侵过程的蛋白酶的发育调节 由人类滋养层细胞 第三个项目确定并描述了 在围着床期小鼠中表达的生长因子和受体 胚胎 第四个项目分析了增长的表现和作用 参与信号传导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 （androgenote）. 第五个项目审查了可持续发展的问题， 植入隐性致死突变体，并表征单体， 小鼠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 小鼠单性生殖和雄生殖的发育失败。 行政核心将提供组织活动， 研究人员之间的互动。 抗体核心将是 负责产生针对抗原的抗体 investigators. 形态学/原位定位核心将是 负责进行光和电子显微镜组织学， 免疫组织化学和信使RNA原位定位 mRNA杂交。 转基因/干细胞核心将负责 用于产生转基因小鼠品系，以及用于进行靶向基因 通过胚胎干细胞中的同源重组进行突变。 重点 小鼠和人类滋养层细胞的联合发育 这些研究结论的普遍性。 本次比较 这种方法应该使新概念在临床上的应用成为可能。 问题，如产前诊断，检测和治疗 滋养层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.