Axes and compartments in the wing of the fruitfly

这份提案概述了一系列实验，旨在测试和完善我们对 发育中的组织精确构图的机制。这样的精确度对于正常的 人类发展，并分析这种模式产生的手段对我们 了解正常的胎儿发育，并开发治疗方法，以从疾病和 受伤。然而，研究人员对脊椎动物发育进行实验分析的能力是有限的， 脊椎动物基因组和胎儿的复杂性。因此，该提案概述了正在进行的一系列 果蝇附肢发育过程中这些问题的分析实验 黑猩猩。在果蝇的翅膀中，特定的组织以一种极其刻板的方式从单一的 上皮细胞层。这个系统不仅简单，而且遗传和分子工具也可用于工作 在果蝇上是任何其他动物系统都无法比拟的。我们将结合使用基因， 用组织化学和分子技术分析定型神经元的发育基础 在果蝇身上发现的发育。我们的分析包括测试一些已知基因和 信号通路，以及寻找对构图过程至关重要的新基因。我们的首要目标是 分析人类Wnt抑制因子-1的同源物--分泌蛋白Shift的作用及其如何 在沿着隔室边界诱导细胞的过程中，会干扰Hedgehog信号。我们的第二个 目的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附素，脂肪和Dachsous， 调节生长和近、远端纹饰。

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.