CELL-CELL ADHESION AMONG EMBRYONIC CELLS

在胚胎发育过程中，细胞通过机械力化学作用聚集在一起。 意味着导致胚胎诱导。这种对环境的依赖 分化依次导致组织和器官的分化。从长远来看 这项提议的目标是分析细胞相互作用如何 胚胎诱导导致正常发育中的形态发生及其机制 这些相互作用的错乱会导致发育缺陷。 由于细胞接触在这些事件中的核心作用，我们的方法 一直致力于鉴定和化学定义化合物的结构和活性 细胞黏附分子(CAM)。现已确定了几个CAMS，并 对这些分子进行了详细的表征和cdna探针研究。 已定义。免疫组织化学研究表明，cam在某些部位表达。 胚胎诱导以及组织和器官的显著阶段 队形。在开发的早期，这个表达遵循了一组明确的 对各种各样的组织都适用的规则。这些观察结果 提示对已定义分子的场所特异性调节介导了 细胞黏附在形态发生和组织发生中的关键过程。 将使用两个主要的补充方法来扩展和深化这一点 结论。第一，凸轮在正常开发中的详细国产化 组织将通过免疫学和基因探针技术和 与已知的发育相互作用和过程相关。第二, 凸轮的功能在不同的发育阶段会受到干扰。 以及由扰动引起的生化和组织学变化 将根据本地化研究进行分析。具体来说，我们 将：(1)详细分析CAM在肝、肾组织中的表达。 肢体、肺和眼科和耳科安慰剂(2)使用抗体来扰动 CaM在这些组织的器官和细胞培养中以及在完整的 胚胎处于发育阶段，此时诱导和形态发生事件 已知发生(3)继续研究以检测、隔离和表征 新的CaM(4)决定了CaM在神经元形成中的作用 小脑和视网膜顶盖系统的联系和(5)利用 皮肤细胞培养产生附属物，如羽毛以及 神经组织外植体，以确定参与控制的因素 对CAM表达的影响。

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.