ANALYSIS OF THE CELL SURFACE IN MAMMALIAN DEVELOPMENT

哺乳动物发育中的细胞表面分析

• 批准号: 3318818
• 负责人: BRUCE S BABIARZ
• 金额: $ 13.7万
• 依托单位: RUTGERS, THE STATE UNIV OF N.J.
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-09-01 至 1993-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3318818
• 关键词: autoradiography; cell adhesion; cell cell interaction; cell differentiation; cell migration; cell type; decidua; electron microscopy; embryo /fetus antigen; embryo /fetus cell /tissue; enzyme mechanism; enzyme substrate; fertilization; galactosyltransferases; gel electrophoresis; gel filtration chromatography; gene expression; histogenesis; hormone receptor; hormone regulation /control mechanism; immunocytochemistry; immunofluorescence technique; immunoprecipitation; laboratory mouse; mammalian embryology; membrane activity; membrane structure; neoplastic growth; scintillation counter; surface antigens

Successful implantation is critical for the successful development of the mammalian embryo. Changes in trophoblast cell adhesion play a major role in this process. The experiments proposed here will investigate the role of the cell surface in the differentiation of trophoblast in mouse ectoplacental cones (EPCs) and study the molecular mechanism involved in its interaction with uterine decidual cells. Previous work has indicated that immature trophoblast cell adhesion is mediated in part by the interaction of surface galactosyltransferase (GalTase) with glycoconjugate substrates. Differentiation to non-adhesive, invasive giant cells results in a downregulation of the GalTase adhesion system, although giant cells still possess surface GalTase activity. The experiments proposed here will continue to examine the role of GalTase in implantation. The hypothesis to be tested is that substrate availability for GalTase mediates trophoblast transition from adhesive to migratory behavior by interacting with extracellular substrates to provide a migratory mechanism. These experiments will use existing or newly produced antibodies to study developmental regulation of the cell surface substrate, determine the role of GalTase in migration on defined matrices, and examine the possibility that the enzyme:substrate interaction provides a signal controlling trophoblast differentiation. Implantation will be further studied using a newly developed in vitro model system. Uterine decidual cells will be used as a substrate for the attachment and spreading of EPC trophoblast. These cultures will be analyzed by electron microscopy and the adhesion systems between trophoblast and decidua analyzed with trypsinization, perturbation, and biochemical techniques. Specific antisera will be produced which identifies the molecules involved in trophoblast:decidua interactions. These studies will provide new information on the cellular and molecular mechanism involved in trophoblast differentiation and mammalian implantation. This information can be applied to the development of technologies to assist infertile couples (IVF and embryo transfer) as well as provide new information on the uterine control of tissue invasion. This information could be applied to the study of uncontrolled invasion associated with malignant cell type.

成功植入对于成功发展至关重要 哺乳动物胚胎。 滋养细胞粘附的变化 在此过程中的主要作用。 这里提出的实验将 研究细胞表面在分化中的作用 小鼠外体锥（EPC）中的滋养细胞并研究 与子宫相互作用涉及的分子机制 decIDual细胞。 以前的工作表明未成熟 滋养细胞的粘附部分由相互作用介导 与糖缀合物的表面半乳糖基转移酶（Galtase）的 基材。 与非粘附性侵入性巨细胞的分化 导致仪表酶粘附系统的下调， 尽管巨细胞仍然具有表面辐射酶活性。 这 这里提出的实验将继续检查 植入中的galtase。 要检验的假设是 Galtase的底物可用性介导滋养细胞过渡 通过与粘合剂到迁移行为 细胞外底物提供迁移机制。 这些 实验将使用现有或新生产的抗体进行研究 细胞表面底物的发育调节，确定 Galtase在迁移中的作用在定义的矩阵上，并检查 酶：底物相互作用的可能性提供了 信号控制滋养细胞分化。 植入将 使用新开发的体外模型系统进一步研究。 子宫判例细胞将用作底物 EPC滋养细胞的附着和扩散。 这些文化会 通过电子显微镜和之间的粘附系统分析 通过胰蛋白酶化，扰动，滋养细胞和Decidua分析 和生化技术。 将产生特定的抗血清 识别参与滋养细胞的分子：decidua 互动。 这些研究将提供有关 细胞和分子机制涉及滋养细胞 分化和哺乳动物植入。 此信息可以 应用于技术的开发以帮助不育 夫妻（IVF和胚胎转移）以及提供新的 有关组织侵袭子宫控制的信息。 这 信息可以应用于不受控制的入侵的研究 与恶性细胞类型相关。