CELL-CELL ADHESION AMONG EMBRYONIC CELLS

细胞粘附分子（CAM）出现在特定的时间和地点 在发展过程中，并管理边界的形成和组织图案。 这就提出了一个假设，即依赖于位置的表达， 结合和信号功能的CAM都是至关重要的 形态发生的调控。 与这一假设雅阁， 结果表明，CAMs的位置依赖性表达， 发育受同源盒（Hox）和配对盒（PAX）基因调控 而细胞间的结合又通过CAM传递信号， 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-细胞结合之后。 在aim I中， 拟议的研究将检查N-CAM细胞外的相互作用， 结构域在homophilic结合，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 和N-CAM激活的星形胶质细胞中基因表达的变化 结合将被检查和比较什么是已知的关于这样的 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的结合强烈 抑制其增殖并诱导差异基因表达。 在目的III中，研究N-CAM的存在或不存在对基因表达的影响。 将通过使用特异性基因探针在体内研究表达， 在缺乏所有形式的N-CAM的敲除小鼠中的消减杂交。 将进行研究，以确定是否缺乏N-CAM 在发育过程中， 多种基因的组织，包括Hox基因、Pax基因和CAM基因， 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.