CELL INTERACTIONS ORGANIZING THE INSECT SEGMENT

发育生物学中的一个基本问题是一个最初未指明的 一片细胞自我组织。 基于相对位置，细胞 差异化以产生广泛多样的形式和模式。 我们 利用果蝇的遗传学， 细胞通过分子和细胞机制在内部组织自己， 段。 系统的遗传筛查已经确定了 极性基因，介导细胞间的相互作用， 维护和完善每个部门的组织。 贴片（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膜蛋白。 基因实验表明 它就像一个受体。 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 实验是：1）为了确定是否一个组合码的段 极性基因表达预测了细胞内的形态决定， 片段 2)确认和扩展交互作用的描述 其组织片段内的细胞。 信号通路是什么 组织这个环节的人吗 3)要确定的最小细胞数 生成完整图案所需的时间。 4)问如何异位 PTC的表达将改变节段模式。 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 膜的 ptc蛋白的物理特性是否与 其职能如上所述？ 6)为了识别其他基因， 在相同或拮抗的信号传导途径中（例如，第二配体 信使）通过它们与PTC的遗传相互作用。 了解 在昆虫节内组织细胞的细胞现象将 回答了发育生物学中的一个基本问题， 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.