CELL INTERACTIONS ORGANIZING THE INSECT SEGMENT

发育生物学中的一个基本问题是，一种最初未指明的 单元格会自行组织起来。基于相对位置，单元格 差异化以产生广泛不同的形式和图案。我们是 利用果蝇的遗传学来理解 细胞在体内组织自身的分子和细胞机制 细分市场。系统的遗传筛查已经确定了这一片段 极性基因，它调节细胞的相互作用， 维护和完善每个细分市场的组织结构。已修补(PTC) 是一个片段极性基因，其推导的氨基酸序列表明 它编码一个大的完整的膜蛋白。基因实验表明 它的功能就像一种受体。我们将使用克隆的PTC基因和其他 克隆片段极性基因作为研究相互作用的工具 组织段内的单元格。建议的具体目标 实验内容为：1)确定一段组合码是否 极性基因表达预测细胞内的形态决定 细分市场。2)确认和扩展交互的描述 其组织分段内的单元。信号通路是什么？ 组织分段？3)以确定最小单元格数量 生成完整图案所需的。4)询问异国情结 PTC的表达将改变节段性模式。5)确定 PTC蛋白产物的亚细胞定位及其在细胞内的拓扑结构 薄膜。PTC蛋白的物理性质是否与 它的功能如上所述？6)以识别其他起作用的基因 在相同或拮抗的信号通路中(例如，配体，第二 信使)通过它们与PTC的遗传相互作用。了解 昆虫节段内组织细胞的细胞现象将 回答发育生物学中的一个基本问题，最终会有所帮助 让我们了解人类的发育障碍。

A basic question in developmental biology is how an initially unspecified sheet of cells organizes itself. Based on relative position, cells differentiate to generate widely diverse forms and patterns. We are exploiting the genetics of the fruit fly, Drosophila, to understand the molecular and cellular mechanisms by which cells organize themselves within the segment. Systematic genetic screens have identified the segment polarity genes, which mediate the cell interactions that establish, maintain and refine the organization within every segment. patched (ptc) is a segment polarity gene whose deduced amino acid sequence suggests that it encodes a large integral membrane protein. Genetic experiments suggest that it functions as a receptor. We will use the cloned ptc gene and other cloned segment polarity genes as tools to study the interactions that organize cells within the segment. The specific aims of the proposed experiments are: 1) To determine whether a combinatorial code of segment polarity gene expression predicts morphological determination within the segment. 2) To confirm and extend the description of the interactions which organize cells within the segment. What are the signalling pathways that organize the segment? 3) To determine the minimum number of cells of required to generate the complete pattern. 4) To ask how ectopic expression of ptc will redirect the segmental pattern. 5) To determine the subcellular location of the ptc protein product and its topology within the membrane. Are the physical properties of the ptc protein consistent with its functions as determined above? 6) To identify other genes which act in the same or antagonistic signalling pathways (e.g., ligands, second messengers) by their genetic interactions with ptc. Understanding the cellular phenomena which organize cells within the insect segment will answer a basic question in developmental biology and will ultimately help us to understand developmental disorders in man.