Axes and compartments in the wing of the fruitfly

果蝇翅膀上的轴和隔间

• 批准号: 7591604
• 负责人: SETH S BLAIR
• 金额: $ 25.3万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-08-01 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7591604
• 关键词: Adhesives; Affect; Alleles; Animals; Anterior; Binding; Biochemical; Biological Assay; Cell Polarity; Cells; Cleaved cell; Development; Disease; Distal; Drosophila genus; Drosophila melanogaster; Epithelial Cells; Erinaceidae; Extracellular Domain; Extracellular Matrix; Extracellular Space; Family; Fatty acid glycerol esters; Fetal Development; Fetus; Genes; Genetic; Genetic Epistasis; Golgi Apparatus; Grant; Growth; Heparan Sulfate Proteoglycan; Homologous Gene; Human; Human Development; Injury; Joints; Ligands; Lipids; Mediating; Modification; Molecular; Molecular Genetics; Movement; Mutate; Mutation; Orthologous Gene; Pathway interactions; Pattern; Phenotype; Play; Process; Proteins; Publishing; Recovery; Regulation; Relative (related person); Research Personnel; Role; Series; Signal Pathway; Signal Transduction; Signaling Pathway Gene; Specific qualifier value; Specificity; Stereotyping; Structure; System; Techniques; Tertiary Protein Structure; Testing; Tissues; Vertebrates; Wing; Wnt proteins; Work; appendage; base; cofactor; design; extracellular; human CYP2B6 protein; member; mutant; neuron development; novel; palmitoylation; programs; receptor; research study; smoothened signaling pathway; therapy development; tool; vertebrate genome

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.

该提案概述了一系列实验，旨在测试和完善我们对 发育中的组织精确形成图案的机制。这种精度对于正常情况来说是必要的 人类的发展，分析这种模式产生的方式对于我们人类发展至关重要 了解正常胎儿发育，并开发疾病康复疗法 受伤。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， 由于脊椎动物基因组和胎儿的复杂性。因此，该提案概述了一系列正在进行的 分析果蝇附属物发育中的这些问题的实验 黑腹果蝇。在果蝇翅膀中，特定的组织以极其刻板的方式从单个组织中产生 上皮细胞层。该系统不仅简单，而且遗传和分子工具可用于工作 果蝇的系统是任何其他动物系统都无法比拟的。我们将结合遗传、 组织化学和分子技术来分析定型神经元的发育基础 在果蝇中发现发育。我们的分析包括测试一些已知基因的作用和 信号通路，并寻找对模式形成过程至关重要的新基因。我们的首要目标是 分析分泌蛋白 Shifted（人类 Wnt 抑制因子 1 的同源物）的作用，以及它如何发挥作用 在沿着区室边界诱导细胞的过程中，与 Hedgehog 信号传导相互作用。我们的第二个 目的是研究一种新颖的信号传导机制，通过该机制，两种不寻常的原钙粘蛋白 Fat 和 Dachsous 调节生长和近远端模式。