Analysis of Early Wing Vein Development in Drosophila

描述（由申请人提供）：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响应产生的位置信息转化为在不同位置形成专门的形态结构。果蝇翅脉发育的起始提供了一个特别有利的条件， 这是一个研究模式化和成人结构形成之间联系的系统。很多是 已经知道了位置是如何沿着翅膀的主轴沿着指定的，以及这些信息如何导致在不同的脉原基中启动脉特异性基因表达模式。这项拨款提案的总体目标是了解位置信息的机制， 转换成第二和第五纵向翅静脉的静脉特异性分化程序，所述第二和第五纵向翅静脉形成于沿翅的前后轴沿着的相对位置。先前的分析显示，静脉形成在沿着细胞邻接域之间的边界的窄线上。静脉原基形成沿着细胞的一个域的边缘响应于从相邻细胞发出的可扩散的短程信号，所述相邻细胞不能响应它们产生的静脉诱导信号。理解这种“仅用于出口”的信号传导模式的中心目标是确定推定的静脉诱导信号的分子身份。除了分析脉形态发生启动的机制外，我们还将比较knirps（kni）和abrupt（ab）基因的活性，它们分别在第二和第五脉原基中组织脉特异性基因表达程序中起关键作用。 拟议的实验在两个方面与人类健康有关。第一，在发展过程中形成线的问题是一个一般过程。因此，从拟议的 实验将适用于许多脊椎动物发育阶段。第二，决定静脉位置的几个基因的缺陷在人类中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有广泛的应用，以了解脊椎动物的发展，以及提供可能的见解人类疾病的机制。

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.