EXTRACELLULAR MATERIALS AND EMBRYONIC ORGAN FORMATION

参与形态发生的细胞行为受 细胞表面的分子将细胞与细胞外结合起来 矩阵和其他细胞。上皮细胞含有一个细胞表面 蛋白多糖，是一种高亲和力的特异性受体 间隙基质材料。蛋白多糖似乎 通过物理连接细胞内来稳定上皮层 间充质细胞产生基质的细胞骨架。 最近的结果导致了一个工作假说，即核心蛋白 在细胞表面的蛋白多糖中，细胞表面的蛋白质 糖胺多糖链是共价结合的，是发育中的一种 作为基质受体或细胞功能的受调控分子 依赖于其翻译后的黏附分子 修改。作为一种基质受体，它会含有肝素和 硫酸软骨素链，在发育后期表达， 在成熟的组织中，仅在简单的 上皮细胞。作为一种细胞黏附分子，它会比 广泛糖基化，在发育早期表达， 在成熟的组织中，围绕着复层的上皮细胞。在.期间 胚胎发生时，它会同时出现在上皮和 间充质细胞，但改变其表达与 形态发生事件。 此应用程序旨在探索这样一种假设： 上皮细胞表面蛋白多糖是一种发育调节因子 多功能黏附分子。具体目标是： (I)评价细胞表面蛋白多糖的调节作用 小鼠早期胚胎及后续序列中的表达 免疫学和分子生物学评价的形态发生事件 它的出现时间，细胞和组织定位，后 翻译修饰和信使核糖核酸水平 (Ii)测试细胞表面蛋白多糖是否具有 一种通过试图扰乱细胞聚集的细胞黏附分子 和组织发生与确定的抗体和配基，以分离 一种内源性配体(S)及其简单修饰的比较 和复层上皮， (Iii)通过检查是否存在基质受体角色来确定 它遍历基底板，将其功能与其他 受体，评估它是否介导受体特异性 细胞反应和产生的细胞有缺陷或 增强了细胞表面的蛋白多糖。 细胞-细胞和细胞-基质相关机制的知识 黏附对于了解细胞至关重要 发育中的行为和肿瘤的侵袭。这项研究 将为这些机制提供新的见解，可能会导致 到诊断、治疗和最终预防出生缺陷 和转移瘤。

The cellular behavior involved in morphogenesis are regulated by molecules at cell surfaces that bind cells to the extracellular matrix and to other cells. Epithelial cells contain a cell surface proteoglycan that is a high affinity receptor specific for interstitial matrix materials. The proteoglycan appears to stabilize epithelial sheets by physically linking the intracellular cytoskeleton with the matrix produced by mesenchymal cells. Recent results lead to the working hypothesis that the core protein of the cell surface proteoglycan, the protein to which the glycosaminoglycan chains are covalently bound, is a developmentally regulated molecule that functions as a matrix receptor or as a cell adhesion molecule depending on its post-translational modifications. As a matrix receptor, it would contain heparan and chondroitin sulfate chains, be expressed late in development and, in mature tissues, be solely on the basolateral surface of simple epithelial cells. As a cell adhesion molecule, it would be less extensively glycosylated, be expressed early in development and, in mature tissues, surround stratified epithelial cells. During embryogenesis, it would be present on both epithelial and mesenchymal cells, but change its expression in association with morphogenetic events. This application is designed to explore the hypothesis that the epithelial cell surface proteoglycan is a developmentally regulated multifunctional adhesion molecule. The specific aims are to: (i) evaluate the regulation of cell surface proteoglycan expression in early mouse embryos and during subsequence morphogenetic events by immunological and molecular assessments of its time of appearance, cell and tissue localization, post- translational modifications and mRNA level, (ii) test whether the cell surface proteoglycan functions as a cell adhesion molecule by attempting to perturb cell aggregation and histogenesis with defined antibodies and ligands, to isolate an endogenous ligand(s) and comparing its modifications in simple and stratified epithelia, (iii) define the matrix receptor role by examining whether it traverses the basal lamina, comparing its function with other receptors, evaluating whether it mediates receptor-specific cellular responses and generating cells that are deficient or enhanced in the cell surface proteoglycan. Knowledge of the mechanisms involved in cell-cell and cell-matrix adhesion is critically important to an understanding of cell behavior during development and neoplastic invasion. This research will provide new insight into these mechanisms, potentially leading to diagnosis, treatment and ultimately, prevention of birth defects and metastases.