Axes and compartments in the wing of the fruitfly

描述（由申请人提供）：该提案概述了一系列实验，旨在测试和完善我们对发育组织精确图案化的机制的理解。这种精确性对正常的人类发育至关重要，分析这种模式产生的方式对我们理解正常的胎儿发育以及开发从疾病和损伤中恢复的治疗方法都至关重要。然而，研究人员通过实验分析脊椎动物发育的能力受到脊椎动物基因组和胎儿复杂性的限制。因此，这项提议概述了一系列正在进行的实验，分析果蝇（Drosophila melanogaster）正在发育的附属物中的这些问题。在果蝇的翅膀中，特定的组织以一种极其定型的方式从单层上皮细胞中产生。这个系统不仅简单，而且可用于果蝇研究的遗传和分子工具是任何其他动物系统无法比拟的。我们将结合遗传学、组织化学和分子生物学技术来分析果蝇中定型神经元发育的发育基础。我们的分析包括测试一些已知基因和信号通路的作用，并寻找对模式化过程至关重要的新基因。我们的第一个目的是分析分泌蛋白移位的作用，人类Wnt抑制因子-1的同源物，以及它如何在诱导细胞沿着隔室边界与刺猬信号相互作用。我们的第二个目标是研究一种新的信号机制，通过这种机制，两种不寻常的原钙粘蛋白，脂肪和Dachsous，调节生长和近端-远端模式。

DESCRIPTION (provided by applicant): This proposal outlines a series of experiments designed to test and refine our understanding of the mechanisms by which the developing tissues precisely patterned. Such precision is essential to normal human development, and analyzing the means by which such patterning arises, is essential to both our understanding of normal fetal development, and for developing therapies for the recovery from disease and injury. The ability of researchers to experimentally analyze development in vertebrates is limited, however, by the complexity of the vertebrate genome and fetus. This proposal therefore outlines an ongoing series of experiments that analyze these problems in the developing appendages of the fruitfly, Drosophila melanogaster. In the fruitfly wing, specific tissues arise in an extremely stereotyped fashion from a single layer of epithelial cells. Not only is this system simple, but the genetic and molecular tools available for work on Drosophila are unmatched by any other animal system. We will use a combination of genetic, histochemical and molecular techniques to analyze the developmental bases of the stereotyped neuronal development found in Drosophila. Our analyses include testing the roles of a number of known genes and signaling pathways, and searching for novel genes critical to the patterning process. Our first aim is to analyze the role of the secreted protein Shifted, a homolog of human Wnt Inhibitory Factor-1, and how it interacts with Hedgehog signaling during the induction of cells along compartment boundaries. Our second aim is examine a novel signaling mechanism by which two unusual protocadherins, Fat and Dachsous, regulate the growth and proximal-distal patterning.