Axes and compartments in the wing of the fruitfly

该提案概述了一系列旨在测试和完善我们对 发育中的组织形成精确图案的机制。这种精确度对于正常的 人类的发展，并分析这种模式产生的方式是必不可少的，我们都有必要 了解正常的胎儿发育，并开发从疾病中恢复的治疗方法， 损伤然而，研究人员通过实验分析脊椎动物发育的能力是有限的， 脊椎动物基因组和胎儿的复杂性。因此，本提案概述了一系列正在进行的 在果蝇的附属器官发育过程中分析这些问题的实验 黑腹菌在果蝇的翅膀中，特定的组织以一种极其定型的方式从一个单一的 上皮细胞层。这个系统不仅简单，而且遗传学和分子学工具 是其他动物系统无法比拟的。我们将结合基因， 组织化学和分子生物学技术分析定型神经元的发育基础 在果蝇中发现的。我们的分析包括测试一些已知基因的作用， 信号通路，并寻找新的基因至关重要的模式化过程。我们的首要目标是 分析分泌蛋白Shifted的作用，它是人类Wnt抑制因子-1的同源物，以及它如何 在细胞沿沿着边界诱导过程中与Hedgehog信号传导相互作用。我们的第二 目的是研究一种新的信号传导机制，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。

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 the 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 seriesof experiments that analyze these problems in the developing appendages of the fruitly, 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 intercts 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.