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，机械化学将细胞聚集在一起 意味着导致胚胎诱导。 这个环境依赖 分化反过来引起组织和器官。 长期 该建议的目标是分析如何 胚胎诱导导致正常发育中的形态发生以及如何 这些相互作用的危险会导致发育缺陷。 由于细胞接触在这些事件中的核心作用，我们的方法 一直在识别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凸轮 这些分子的详细表征和cDNA探针已经 定义。 免疫组织化学研究表明，凸轮在位置表达 胚胎诱导以及组织和器官的显着阶段 形成。 在开发的早期，这种表达遵循一套确定的 规则是多种组织的一般规则。 这些观察 表明定义分子的本地特异性调节介导 细胞粘附在形态发生和组织发生中的关键过程。 将使用两种主要补充方法来扩展和加深此 结论。 首先，在正常开发中详细的凸轮本地化 组织将通过免疫学和基因探针技术进行，以及 与已知的发展相互作用和过程相关。 第二， 凸轮的功能将在开发的不同阶段受到干扰 以及扰动引起的生化和组织学变化 将根据本地化研究来分析。 特别是我们 威尔：（1）详细分析肝脏中的CAM表达，肾脏， 肢体，肺，视线和耳片置换（2）使用抗体扰动 凸轮在这些组织的器官和细胞培养物中的功能以及完整的 当感应和形态发生事件是发育阶段的胚胎 已知发生（3）继续研究以检测，分离和表征 新凸轮（4）确定凸轮在神经元形成中的作用 小脑和视网膜直肠系统的连接，（5）使用 皮肤细胞的培养物产生附属物，例如羽毛以及 神经组织外植体以定义与对照有关的因素 CAM表达。