ANALYSIS OF THE CELL SURFACE IN MAMMALIAN DEVELOPMENT

成功的植入是成功发育的关键 哺乳动物的胚胎。 滋养层细胞粘附作用的变化 在这一过程中发挥重要作用。 这里提出的实验将 研究细胞表面在细胞分化中的作用， 小鼠胎盘外锥（EPCs）的滋养层，并研究 与子宫内膜相互作用的分子机制 蜕膜细胞 以前的研究表明， 滋养层细胞的粘附部分是由 表面半乳糖基转移酶（GalTase）与糖缀合物 印刷受体. 分化为非粘附性、侵袭性巨细胞 导致GalTase粘附系统的下调， 尽管巨细胞仍具有表面半乳糖苷酶活性。 的 这里提出的实验将继续研究的作用， GalTase植入。 有待检验的假设是， GalTase底物可利用性介导滋养层转变 从粘附到迁移行为， 细胞外基质，以提供迁移机制。 这些 实验将使用现有的或新产生的抗体来研究 细胞表面基质的发育调节，决定 GalTase在定义基质迁移中的作用，并检查 酶：底物相互作用提供 控制滋养层分化的信号。 植入将 使用新开发的体外模型系统进行进一步研究。 子宫蜕膜细胞将用作 EPC滋养层细胞的附着和伸展。 这些文化将 通过电子显微镜和粘附系统之间进行分析， 用胰蛋白酶消化，扰动， 和生化技术。 将产生特异性抗血清 识别滋养层中的分子： 交互. 这些研究将提供有关 滋养层的细胞分子机制 分化和哺乳动物植入。 该信息可以 应用于技术的发展，以帮助不孕不育 夫妇（IVF和胚胎移植）以及提供新的 关于子宫控制组织侵入的信息。 这 这些信息可以用于研究不受控制的入侵 与恶性细胞类型相关。

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.