CELL-CELL ADHESION AMONG EMBRYONIC CELLS

胚胎细胞之间的细胞粘附

• 批准号: 2196681
• 负责人: GERALD EDELMAN
• 金额: $ 36.99万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-07-01 至 1996-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2196681
• 关键词: Xenopus; alternatives to animals in research; antibody formation; autoradiography; binding proteins; brain metabolism; cell adhesion; cell adhesion molecules; cell aggregation; cell cell interaction; cell migration; chick embryo; complementary DNA; electron microscopy; embryo /fetus cell /tissue; enzyme mechanism; gel electrophoresis; gel filtration chromatography; glia; glycoproteins; growth /development; immunochemistry; immunodiffusion; immunologic techniques; laboratory mouse; laboratory rabbit; mammalian embryology; membrane activity; membrane proteins; monoclonal antibody; neurons; nonmammalian vertebrate embryology; nucleic acid hybridization; nucleic acid probes; protein sequence; retina; single cell analysis; trypsin

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.

在胚胎发育过程中，细胞通过机械化学作用聚集在一起 是指导致胚胎诱导。 这种依赖环境的 分化又产生组织和器官。 长期来看 该提案的目标是分析细胞之间的相互作用如何 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 已识别并化学定义结构和活性 细胞粘附分子（CAM）。 现已确定多个 CAMS，并 详细描述了这些分子的 cDNA 探针 定义的。 免疫组织化学研究表明 CAM 在位点表达 胚胎诱导以及组织和器官的显着阶段 形成。 在开发早期，该表达式遵循一组明确的 对多种组织通用的规则。 这些观察 表明特定分子的局部特异性调节介导 细胞粘附在形态发生和组织发生中的关键过程。 将使用两种主要的互补方法来扩展和深化这一 结论。 一、正常开发中CAM的详细定位 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、 肢体、肺以及视、耳基板 (2) 使用抗体来干扰 CAM 在这些组织的器官和细胞培养物以及完整的细胞中发挥作用 当诱导和形态发生事件发生时，胚胎处于发育阶段 已知发生的情况 (3) 继续研究以检测、分离和表征 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中的连接以及（5）利用 皮肤细胞培养物产生羽毛等附属物以及 神经组织外植体以确定参与控制的因素 CAM 表达。