STEPS CONTROLLING GENE EXPRESSION

由母体终端系统编码的细胞信号通路，以及 与哺乳动物的PDGF激活途径有惊人的相似之处 在果蝇胚胎的两极都是活跃的。在 在后部，这条通路需要建立一个基本上不分段的 领地，泰森。在前面，形态梯度，由以下组成 双核(BCD)转录因子，与末端系统相互作用 建立不分段的Acron而不是Telson。关键受精卵 在这些结构域中激活的基因是无尾(Tll)，它编码 一种类固醇受体样的假定转录因子。要了解 建立头部在前部而不是尾部，我们将 描述前侧TLL的BCD控制特征。我们将确定，使用 在体外和体内技术中，TLL中的BCD蛋白结合部位 启动子，并表征它们与终端系统的相互作用。至 了解未分段的域是如何细分的，我们将调查 基因活性在后部的等级。这将首先涉及到 TLL蛋白结合部位的体内外测定 推测的靶基因(包括被Tll激活和抑制的基因)。 因为已知的后部所需的基因如此之少，我们将 进行遗传筛查以识别终端的其他成员 层级，并将描述的和新发现的基因放入一条途径中。 更详细地了解由细胞激活的基因表达 信号通路应该有助于我们对可能 在肿瘤的发生过程中精神错乱。此外，越来越明显的是，这两个人 发育控制的一般机制，甚至是特定的基因 已经在果蝇身上发现的胚胎发育所需的 脊椎动物中的同系物。通过描述所需的遗传层次结构 将胚胎领域细分为更小的、未分割的区域(如 发生在脊椎动物的背腹轴、肢芽和视网膜) 增加我们对位置信息产生机制的了解 演绎和提炼。最终，这将使我们了解 人类先天缺陷的遗传学和细胞学基础。

A cell signalling pathway, encoded by the maternal terminal system and bearing striking similarity to the PDGF-activated pathway in mammalian systems, is active at both poles of the Drosophila embryo. In the posterior, this pathway is required to establish a largely unsegmented domain, the telson. In the anterior, a morphogen gradient, consisting of the bicoid (bcd) transcription factor, interacts with the terminal system to establish the nonsegmented acron instead of a telson. The key zygotic gene activated in each of these domains is tailless (tll), which encodes a steroid receptor-like putative transcription factor. To understand the establishment of head at the anterior rather than tail, we will characterize bcd control of tll in the anterior. We will determine, using both in vitro and in vivo techniques, bcd protein binding sites in the tll promoter, and characterize their interaction with the terminal system. To understand how a nonsegmented domain is subdivided, we will investigate the hierarchy of gene activity in the posterior. This will first involve determination, in vitro and in vivo, of tll protein binding sites in presumed target genes (both those activated and those repressed by tll). Because so few genes are known that are required in the posterior, we will carry out genetic screens to identify additional members of the terminal hierarchy, and place described and newly discovered genes into a pathway. Understanding in greater detail the gene expression activated by a cell signalling pathway should contribute to our knowledge of genes that might be deranged in oncogenesis. Also, it is becoming evident that both general mechanisms of developmental control, and even specific genes required in embryogenesis, that have been identified in Drosophila have homologs in vertebrates. By characterizing a genetic hierarchy required to subdivide an embryonic field into smaller, nonsegmented domains (as occurs in the vertebrate dorsal-ventral axis, limb bud and retina) we will increase our knowledge of mechanisms by which positional information is interpreted and refined. Ultimately this will allow us to understand the genetic and cellular basis of human birth defects.