ANALYSIS OF EARLY WING VEIN DEVELOPMENT IN DROSPHILIA

描述(改编自调查人员摘要)：这项工作的长期目标 建议是了解果蝇翅膀静脉发育是如何启动的 翼想象盘。果蝇翅膀的长度有五条主脉。我们 提出了翼脉的发育始于 位于前-后(A/P)轴上的细胞的不同区域 三龄幼虫的翅形成盘。在我们令人信服的情况下 假设，我们已经提供了各种证据表明发展 第二纵静脉(L2)的前半部正位于阔静脉前 表达锌指转录因子的细胞的中心结构域 Spalt-大调(Salm)。我们已经提出了SALM表达细胞发出一个信号 激活激素受体家族的表达 KNI/KNRL相关基因编码的转录因子 轨迹。然后，KNI和KNRL基因起到组织基因表达的作用 在L2静脉原基周围。在这项提案中，我们试图了解 表达SALM的细胞激活KNI和KNR1表达的机制 通过分析Knilnrl的一个增强子元件来相邻前细胞 驱动L2原基表达的基因座。我们还建议 研究第二个基因的调节，突变(Ab)，它的功能是 组织L5静脉的形成。在一个关键的实验中，我们建议确定 KNI~NRL和ab基因是否定义了特定的静脉类型(即L2和L5) 或者它们是否更普遍地起到促进静脉而不是静脉间的作用 命运。这些研究对于理解这一基础具有广泛的医学意义。 先天缺陷。因为细胞-细胞信号的缺陷与疾病有关 例如癌症，拟议中的研究也与此类疾病有关 因为L2静脉的发育很大程度上依赖于细胞间的通讯。 此外，与转化生长因子-8相关的信号和EGF-R信号通路也发挥着作用 在维持和提炼静脉花纹方面的突出作用。因为 这些已知途径的错误调控会导致侵袭性形式的癌症， 了解这些通路的调节也具有重要意义 致癌。

DESCRIPTION (adapted from investigator's abstract): The long term goal of this proposal is to understand how wing vein development is initiated in Drosophila wing imaginal discs. Five major veins run the length of the Drosophila wing. We have proposed that wing vein development is initiated at boundaries between distinct domains of cells situated along the anterior-posterior (A/P) axis of the wing imaginal disc in third instar larvae. In our convincing case for this hypothesis, we have provided a variety of evidence indicating that development of the second longitudinal vein (L2) is induced just anterior to a broad central domain of cells expressing a zinc finger transcription factor known as spalt- major (salm). We have proposed that salm expressing cells send a signal to adjacent anterior cells to activate expression of hormonereceptor family transcription factors encoded by genes at the knirpslknirps-related (kni/knrl) locus. The kni and knrl genes then function to organize gene expression in and around the L2 vein primordium. In this proposal we seek to understand the mechanism by which salm expressing cells activate kni and knrl expression in neighboring anterior cells by analyzing an enhancer element of the knilknrl locus which drives expression in the L2 primordium. We also propose to investigate the regulation of a second gene, abrupt (ab), which functions to organize formation of the L5 vein. In a key experiment, we propose to determine whether the kni~nrl and ab genes define specific vein types (i.e. L2 versus L5) or whether they function more generally in promoting vein versus intervein fates. These studies are of broad medical relevance to understanding the basis of birth defects. As defects in cell-cell signaling are involved in disease states such as cancer, the proposed studies also are relevant to such diseases since development of the L2 vein depends critically on cell-cell communication. In addition, the TGF-8 related signaling and EGF-R signaling pathways play prominent roles in maintaining and refining the vein pattern. Because mis-regulation of these known pathways causes aggressive forms of cancer, understanding the regulation of these pathways also is of significant relevance to cancer.