CELL-CELL ADHESION AMONG EMBRYONIC CELLS

细胞黏附分子(CAM)在特定的时间和地点出现 在发育过程中，并管理边缘形成和组织图案形成。 这提示了一种假设，即依赖于位置的表达， 凸轮的绑定和信号传递功能对于 形态发生的调控。根据这一假设，最近 结果表明，在细胞周期中，CAMS的表达具有位置依赖性。 发育受同源盒(HOX)和配对盒(PAX)基因调控 而细胞与细胞的结合又由凸轮细胞传递信号到 影响基因表达的核，包括CAM的表达 基因本身。调查人员研究的目标是 分析细胞信号和基因表达的变化 在N-CAM介导的细胞-细胞结合后发生。在AIM I中， 拟议的研究将检查N-CAM细胞外的相互作用 同源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AIM II中，信号通路 N-CAM激活星形胶质细胞基因表达的变化 我们将检查绑定，并将其与已知的此类绑定进行比较 神经元的路径和变化。此方法基于 N-CAM及其结构域与星形胶质细胞的强结合 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 将通过使用特定的基因探针和 缺失所有形式N-CAM的基因敲除小鼠的消减杂交。 将进行研究，以确定是否没有N-CAM 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。

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.