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）出现在特定时间和地点 在开发和控制边界形成和组织模式的过程中。 这促使以下假设：位置依赖性表达， 绑定和凸轮的信号传导函数对于 形态发生的调节。 根据这个假设，最近 结果表明，凸轮的位置依赖性表达 开发受Homebox（HOX）和配对盒（PAX）基因调节 凸轮依次将信号发送到 影响基因表达的细胞核，包括CAM的表达 基因本身。 调查人员研究的目的是 分析细胞信号传导和基因表达的变化 在由N-CAM介导的细胞细胞结合后发生。 在目标一世中 拟议的研究将检查N-CAM细胞外的相互作用 同性结合期间的结构域并确定细胞内 N-CAM细胞质结构域的相互作用。 在AIM II中，信号途径 N-CAM激活的星形胶质细胞中基因表达的变化 将检查绑定，并将其与有关此类的已知内容进行比较 途径和神经元的变化。 这种方法基于 发现N-CAM及其域与星形胶质细胞的结合非常强烈 抑制它们的增殖并诱导差异基因表达。 在AIM III中，N-CAM的存在或不存在对基因的影响 通过使用特定基因探针和 缺乏所有形式的N-CAM的基因敲除小鼠中的减法杂交。 将进行研究以确定是否没有N-CAM 在开发过程中特别影响表达模式 多种基因的组织，包括HOX基因，PAX基因和CAM 基因本身。