ANALYSIS OF EARLY WING VEIN DEVELOPMENT IN DROSPHILIA

描述（改编自研究者摘要）：本研究的长期目标 我们的建议是要了解果蝇的翅脉发育是如何开始的 翅成虫盘。果蝇翅膀上有五条主要的静脉。我们 已经提出，翼静脉的发展开始于 位于沿着前后（A/P）轴的细胞的不同区域 三龄幼虫的翅盘。在我们有说服力的情况下 假设，我们已经提供了各种证据表明，发展 第二纵静脉（L2）的诱导位置位于宽静脉（L2）的正前方， 表达锌指转录因子的细胞的中心结构域， 斯帕尔特-大调（Salm）。我们已经提出表达salm的细胞发送信号 与邻近的前细胞连接以激活受体家族的表达 由knirpslknirps相关基因编码的转录因子（kni/knrl） 基因座kni和knrl基因的功能是组织基因表达， 在L2静脉原基周围。在本建议中，我们试图理解 表达salm的细胞激活kni和knrl表达的机制 通过分析knilknrl的增强子元件 在L2原基中驱动表达的基因座。我们亦建议 研究第二个基因突变（ab）的调控，其功能是 形成L5静脉。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对L5） 或者它们是否更普遍地在促进静脉与静脉间 命运这些研究对于理解 出生缺陷。由于细胞间信号传导的缺陷与疾病有关， 例如癌症，拟议的研究也与这些疾病有关。 因为L2静脉的发育关键取决于细胞间通讯。 此外，TGF-8相关的信号传导和EGF-R信号传导途径在细胞凋亡中起作用。 在保持和细化纹理模式方面的突出作用。因为 这些已知途径的错误调节导致侵袭性形式的癌症， 了解这些途径的调节也具有重要意义 到癌症

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.