CELL-CELL ADHESION AMONG EMBRYONIC CELLS

胚胎细胞之间的细胞粘附

• 批准号: 6125599
• 负责人: GERALD EDELMAN
• 金额: $ 37.47万
• 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 2001-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6125599
• 关键词: affinity chromatography; astrocytes; cell adhesion; cell cell interaction; cell growth regulation; chemical binding; embryo /fetus cell /tissue; embryo /fetus tissue /cell culture; embryogenesis; genetically modified animals; laboratory mouse; mammalian embryology; neural cell adhesion molecules; neurons; protein structure function

Cell adhesion molecules (CAMs) appear at specific times and places during development and govern border formation and tissue patterning. This prompts the hypothesis that the place-dependent expression, binding, and signaling functions of CAMs are all critical for the regulation of morphogenesis. In accord with this hypothesis, recent results indicated that the place-dependent expression of CAMs during development is regulated by homebox (Hox) and paired box (PAX) genes and that cell-cell binding medicated by CAMs in turn sends signals to the nucleus to affect gene expression including the expression of CAM genes themselves. The goal of the investigators' studies is to analyze the changes in cellular signaling and gene expression that occur after cell-cell binding mediated by N-CAM. In aim I, the proposed studies will examine the interaction of N-CAM extracellular domains during homphilic binding and determine the intracellular interactions of N-CAM cytoplasmic domains. In aim II, signal pathways and changes in gene expression in astrocytes activated by N-CAM binding will be examined and compared to what is known about such pathways and changes in neurons. This approach is based on the finding that binding of N-CAM and its domains to astrocytes strongly inhibits their proliferation and induces differential gene expression. In aim III, the effects of the presence or absence of N-CAM on gene expression will be studied in vivo by using specific gene probes and subtractive hybridization in knockout mice lacking all forms of N-CAM. Studies will be carried out to determine whether the absence of N-CAM during development affects the expression patterns in particular tissues of a variety of genes, including Hox genes, Pax genes, and CAM genes themselves.

细胞粘附分子 (CAM) 在特定时间和地点出现 在发育过程中并控制边界形成和组织图案。 这提示了位置相关表达的假设， CAM 的结合和信号传导功能对于 形态发生的调节。 根据这一假设，最近 结果表明，CAMs 的表达具有地点依赖性。 发育受同源盒 (Hox) 和配对盒 (PAX) 基因调控 CAM 介导的细胞间结合反过来向 细胞核影响基因表达，包括 CAM 的表达 基因本身。 研究人员的研究目标是 分析细胞信号传导和基因表达的变化 发生在 N-CAM 介导的细胞与细胞结合之后。 在目标 I 中， 拟议的研究将检查 N-CAM 细胞外的相互作用 同亲结合过程中的结构域并确定细胞内 N-CAM 胞质结构域的相互作用。 在目标 II 中，信号通路 N-CAM 激活的星形胶质细胞基因表达的变化 将检查结合并与已知的此类情况进行比较 神经元的通路和变化。 该方法基于 发现 N-CAM 及其结构域与星形胶质细胞强烈结合 抑制其增殖并诱导差异基因表达。 在目标 III 中，N-CAM 的存在或不存在对基因的影响 将使用特定的基因探针在体内研究表达 缺乏所有形式 N-CAM 的基因敲除小鼠的消减杂交。 将进行研究以确定 N-CAM 是否缺失 在发育过程中尤其会影响表达模式 多种基因的组织，包括 Hox 基因、Pax 基因和 CAM 基因本身。