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，将细胞与细胞外的 基质和其他细胞。 上皮细胞含有细胞表面 蛋白聚糖，其是特异于以下的高亲和力受体 间隙基质材料 蛋白多糖似乎 通过物理连接细胞内 细胞骨架与间充质细胞产生的基质。 最近的结果导致了一个工作假设，即核心蛋白 细胞表面蛋白聚糖的蛋白质， 糖胺聚糖链是共价结合的，是一种发育上的 作为基质受体或细胞发挥功能的受调节分子 粘附分子依赖于其翻译后 修改.作为基质受体，它含有乙酰肝素， 硫酸软骨素链，在发育后期表达， 在成熟组织中，仅在简单的基底外侧表面上， 上皮细胞 作为一种细胞粘附分子， 广泛糖基化，在发育早期表达， 在成熟组织中，围绕着复层上皮细胞。 期间 胚胎发生时，它会出现在上皮细胞和 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以下假设： 上皮细胞表面蛋白聚糖是一种发育调节的 多功能粘附分子。 具体目标是： (i)评价细胞表面蛋白多糖的调节 在小鼠早期胚胎中的表达和在随后的 通过免疫学和分子评估的形态发生事件 其出现时间、细胞和组织定位、后 翻译修饰和mRNA水平， (ii)测试细胞表面蛋白聚糖是否作为 一种细胞粘附分子， 和组织发生，以分离 内源性配体，并在简单的 和复层上皮， (iii)确定基质受体的作用， 它穿过基底层，与其他细胞相比， 受体，评估其是否介导受体特异性 细胞反应和产生细胞是缺乏或 在细胞表面蛋白聚糖中增强。 了解细胞-细胞和细胞-基质的机制 粘附对于理解细胞的 发育过程中的行为和肿瘤侵袭。 本研究 将为这些机制提供新的见解， 诊断、治疗并最终预防出生缺陷 和转移。

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.