Analysis of Early Wing Vein Development in Drosophila

描述(申请人提供)：发育生物学中的一个重要问题是如何将由对可扩散信号的阈值反应产生的位置信息转化为不同位置的特殊形态结构的形成。果蝇翅膀静脉发育的启动为研究模式形成和成体结构形成之间的这种联系提供了一个特别有利的系统。许多人已经知道如何沿着翅膀的主轴指定位置，以及这些信息如何导致不同静脉原基中特定于静脉的基因表达模式的启动。这项赠款提案的总体目标是了解位置信息转换为第二和第五纵翼静脉的特定静脉分化程序的机制，这些静脉形成于机翼前后轴上的相反位置。先前的分析表明，静脉沿着细胞邻接区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的边缘形成，以响应邻近细胞发出的可扩散的短程信号，这些细胞无法对它们产生的静脉诱导信号做出反应。理解这种“仅供出口”的信号模式的一个中心目的是确定假定的静脉诱导信号的分子同一性。除了分析叶脉形态发生的启动机制外，我们还将比较Knirps(Knirps)和ab(Ab)基因的活性，这两个基因分别在第二和第五脉原基中组织叶脉特异的基因表达程序。 拟议中的实验在两个方面与人类健康有关。第一，发展中的线条问题是一个普遍的过程。因此，从拟议的实验中获得的见解将适用于脊椎动物的许多发育阶段。其次，决定静脉位置的几个基因的缺陷在人类发生突变时会导致出生缺陷或癌症。因此，从这些研究中获得的知识应该在理解脊椎动物的发育以及为人类疾病的机制提供可能的见解方面有广泛的应用。

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.