CELL-CELL ADHESION AMONG EMBRYONIC CELLS

在胚胎发育过程中，细胞通过机械化学作用聚集在一起， 意味着导致胚胎诱导。 这种环境依赖性 分化又产生组织和器官。 长期 该提案的目标是分析细胞的相互作用， 胚胎诱导导致正常发育中的形态发生以及如何 这些相互作用的紊乱引起发育缺陷。 由于细胞接触在这些事件中的核心作用，我们的方法 已经确定和化学定义的结构和活动 细胞粘附分子（CAM）。 现在已经确定了几个CAMS， 这些分子的cDNA探针已经被详细表征， 定义了 免疫组织化学研究表明，CAM表达的位点 胚胎诱导以及组织和器官的显著阶段 阵 在发展的早期，这个表达式遵循一组确定的 对各种组织都通用的规则。 这些观察结果 表明特定分子的区域特异性调节介导了 在形态发生和组织发生中细胞粘附的关键过程。 将采用两种主要的互补办法来扩大和深化这一点。 结论 首先，对CAM在常规开发中的具体定位进行了分析 组织将通过免疫学和基因探针技术进行， 与已知的发育相互作用和过程相关。 第二、 CAM的功能在不同的发展阶段会受到干扰 以及由扰动引起的生物化学和组织学变化 将根据本地化研究进行分析。 另外还 将：（1）详细分析CAM在肝、肾、 肢体、肺以及视和耳基板（2）使用抗体干扰 CAM在这些组织的器官和细胞培养物中以及在完整的 胚胎在发展阶段时，诱导和形态发生事件是 已知发生（3）继续研究以检测、分离和表征 新的CAM（4）确定CAM在神经元形成中的作用 小脑和视网膜顶盖系统的连接，以及（5）利用 皮肤细胞的培养产生附属物，如羽毛， 神经组织外植体，以确定参与控制的因素 CAM表达。

During embryonic development, cells are brought together by mechanochemical means resulting in embryonic induction. This milieu-dependent differentiation gives rise in turn to tissues and organs. The long term goal of this proposal is to analyze how the cellular interactions of embryonic induction lead to morphogenesis in normal development and how derangements of these interactions give rise to developmental defects. Because of the central role of cell contact in these events, our approach has been to identify and chemically define the structure and activities of cell adhesion molecules (CAMs). Several CAMS have now been identified and characterized in detail and cDNA probes for these molecules have been defined. Immunohistochemical studies show that CAMs are expressed at sites of embryonic induction as well as at salient stages of tissue and organ formation. Early in development, this expression follows a definite set of rules which are general to a great variety of tissues. These observations suggest that locale-specific regulation of defined molecules mediates the pivotal process of cell adhesion in morphogenesis and histogenesis. Two main complementary approaches will be used to extend and deepen this conclusion. First, detailed localization of CAMs in normally developing tissues will be carried out by immunological and gene probe techniques and correlated with known developmental interactions and processes. Second, the function of CAMs will be perturbed at different stages of development and the biochemical and histological changes caused by the perturbations will be analyzed in light of the localization studies. Specifically we will: (1) make a detailed analysis of CAM expression in liver, kidney, limb, and lung and in optic and otic placodes (2) use antibodies to perturb CAM functions in organ and cell cultures of these tissues and in the intact embryo at stages of development when inductive and morphogenetic events are known to occur (3) continue studies to detect, isolate, and characterize new CAMs (4) determine the role of CAMs in the formation of neuronal connections in the cerebellum and the retinotectal system and (5) utilize cultures of skin cells producing appendages such as feathers as well as nervous tissue explants to define factors that are involved in the control of CAM expression.