Compartment Boundaries in the Wing of the Fruitfly

这项建议概述了一系列实验，旨在测试和完善我们对发育中组织精确构图的机制的理解。这种精确度对正常的人类发育至关重要，而分析这种模式产生的方式对于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是至关重要的。然而，脊椎动物基因组和胚胎的复杂性限制了研究人员对脊椎动物发育进行实验分析的能力。因此，这项提案概述了正在进行的一系列实验，这些实验分析了果蝇黑腹果蝇的发育中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刻板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所无法比拟的。我们将使用遗传、组织化学和分子技术的组合来分析果蝇中发现的刻板印象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，以及寻找对构图过程至关重要的新基因。我们的具体目标是分析翅膀中大间隔谱系限制的形成，以及细胞间信号在形成和维持这些谱系限制中所起的作用。我们将：1：研究隔室特异性“选择器”基因表达的作用和调控机制。2.研究哪些信号负责细胞亲和力的边界特定状态。3.检查哪些细胞行为维持了谱系限制，并基于这些行为开发了生物测定方法。4.使用遗传筛选和生物测定来研究隔室和边界特异性细胞亲和力的分子机制。

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 series of experiments that analyze these problems in the developing appendages of the fruit fly, 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 specific aims are to analyze the formation of the large compartmental lineage restriction in the wing, and the roles played by intercellular signaling in forming and maintaining those lineage restrictions. We will: 1: Investigate the mechanisms by which compartment-specific "selector" gene expression acts and is regulated. 2. Examine which signals are responsible for boundary-specific states of cell affinities. 3. Examine which cell behaviors maintain the lineage restrictions and develop bioassays based on those behaviors. 4. Use genetic screens and bioassays to investigate the molecular mechanisms underlying compartment and boundary-specific cell affinities.