Analysis of Early Wing Vein Development in Drosophila

描述（由申请者提供）：发育生物学中的一个重要问题是如何将对扩散信号的阈值反应产生的位置信息转化为不同位置的专门形态结构的形成。果蝇翼静脉发育的开始为研究成体结构的模式和形成之间的联系提供了一个特别有利的系统。关于翼轴上的位置是如何确定的，以及这些信息是如何导致不同静脉原基中静脉特异性基因表达模式的启动的，我们已经知道了很多。这项拨款提案的总体目标是了解第二和第五纵翼静脉的位置信息转化为静脉特异性分化程序的机制，这两个纵向翼静脉沿着机翼的前后轴形成在相反的位置。先前的分析显示，静脉沿着相邻细胞域之间的边界形成狭窄的线条。静脉原基沿着细胞的一个区域边缘形成，以响应来自相邻细胞的扩散短距离信号，而相邻细胞无法对其产生的静脉诱导信号做出反应。理解这种“仅用于输出”的信号模式的一个中心目标是确定假定的静脉感应信号的分子身份。除了分析静脉形态发生的启动机制外，我们还将比较knirps（kni）和突变（ab）基因的活性，这两个基因分别在组织第二和第五静脉原基的静脉特异性基因表达程序中起关键作用。

DESCRIPTION (provided by applicant): An important problem in developmental biology is how positional information created by threshold responses to diffusible signals is translated into the formation of specialized morphological structures at different locations. The initiation of wing vein development in Drosophila provides a particularly favorable system for investigating this link between patterning and formation of adult structures. A great deal is already known about how positions are specified along the primary axes of the wing and how this information leads to initiation of vein-specific patterns of gene expression in different vein primordia. The overall goal of this grant proposal is to understand the mechanism by which positional information is converted into vein specific differentiation programs for the second and fifth longitudinal wing veins, which form at opposite positions along the anterior-posterior axis of the wing. Previous analysis revealed that veins form in narrow lines along boundaries between abutting domains of cells. Vein primordia form along the edge of one domain of cells in response to diffusible short range signals emanating from adjacent cells that are unable to respond to the vein inducing signal they produce. A central aim in understanding this "for-export-only" mode of signaling is to determine the molecular identity of the putative vein inductive signals. In addition to analyzing the mechanisms by which vein morphogenesis is initiated, we will also compare the activities of the knirps(kni) and abrupt (ab) genes, which play key roles in organizing vein specific gene expression programs in the second and fifth vein primordia respectively. The proposed experiments are relevant to human health in two ways. First, the problem of forming lines during development is a general process. Consequently, insights gained from the proposed experiments will be applicable to many vertebrate stages of development. Second, defects in several genes involved in determining the positions of veins cause birth defects or cancer when mutated in humans. Thus, knowledge gained from these studies should have broad applications to understanding vertebrate development as well as offering possible insights into mechanisms of human disease.