Regeneration of Imaginal Discs in Drosophila

果蝇成虫盘的再生

• 批准号: 7364103
• 负责人: Gerold A. Schubiger
• 金额: $ 9.64万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-05-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7364103
• 关键词: Address; Adult; Affect; Air; Animals; Area; Biological Assay; Biological Models; Candidate Disease Gene; Cell Lineage; Cell division; Cells; Cellular biology; Clone Cells; Condition; Data; Development; Dose; Drosophila genus; Embryonic Development; Enhancers; Ensure; Environment; Event; Exhibits; Frequencies; Generations; Genes; Genetic; Genetic Enhancer Element; Goals; Homeostasis; Injury; Interstitial Collagenase; Larva; Lectin; Life; Link; Liver Regeneration; Maintenance; Mediating; Microarray Analysis; Modification; Molecular; Molecular Profiling; Moon; Mus; Mutation; Natural regeneration; Normal tissue morphology; Numbers; Orthologous Gene; Pathway interactions; Pattern; Personal Satisfaction; Phenotype; Property; Protein Overexpression; Proteins; Reproduction; Role; Signal Pathway; Signal Transduction; Site; Spottings; Stem cells; Testing; Time; Tissues; Twin Multiple Birth; Work; Zebrafish; base; cell behavior; chromatin remodeling; computerized data processing; daughter cell; human disease; imaginal disc; insight; multipotent cell; mutant; novel; repaired; research study

Drosophila imaginal discs are able to regenerate and thus provide us with a model system to study multipotency of cells. Under certain conditions a small set of cells in the "weak point" of each imaginal disc change their fate. This switch, known as transdetermination (TD), occurs with high frequency when wg is overexpressed or when a disc is cut through the "weak point". Expression profiling of these cells identified candidate genes which in functional tests significantly modified TD. Some of these candidates are chromatin-remodeling genes. Furthermore, we identified putative regeneration genes such as air-like, a gene orthologous to the mouse gene augmenter of liver regeneration (air), Matrix metalloproteinase 1 (Mmp1), and dReg, a novel gene that contains a C-lectin domain, Although the mammalian orthologs of these three genes have been linked to regeneration of specific tissues, the mechanism by which they act is not well understood. We propose to continue and complete the functional tests, including the generation of mutations in novel candidate Drosophila genes. Dr. Moon we will test homologous zebrafish genes. In examining regeneration, the issue of stem cells must be addressed. Do TD cells divide like stem cells? Cell clones will be induced'in TD cells to assay for asymmetrical divisions, a landmark of stem cell behavior. These analyses will then be performed in the presence and absence of characterized enhancers and suppressors of TD to test whether these genes affect developmental plasticity by modifying the cell lineage pattern, the number of founder cells or the cell-doubling times. This proposal will contribute to the understanding of which molecular signals increase regeneration potential to ensure normal tissue maintenance and repair. Short summary A few specific cells in each imaginal disc of Drosophila have stem cell properties. If challenged by injury they regenerate. We will test whether these cells divide asymmetrically, a landmark of stem-cell behavior. In addition, we will identify the genes that mediate developmental plasticity and test how their gene products affect multipotent cells and their surroundings. Drosophila has been used as a model system to study human disease and we see here an opportunity to gain insight into stem-cell biology and regeneration.

果蝇成虫盘能够再生，因此为我们提供了一个研究的模型系统 细胞的多能性。在某些条件下，在每个成虫盘的“弱点”中的一小部分细胞 改变他们的命运。这种开关，称为transdetermination（TD），当wg为 过度表达或当椎间盘通过“薄弱点”切开时。这些细胞的表达谱鉴定 在功能测试中显著修饰TD的候选基因。其中一些候选人是 染色质重塑基因此外，我们确定了假定的再生基因，如空气样， 与小鼠肝再生基因增强因子（air）、基质金属蛋白酶1基因同源 （Mmp 1）和dReg，一种含有C-凝集素结构域的新基因，尽管哺乳动物的直向同源物Mmp 1和dReg的同源物Mmp 1的同源物M 这三个基因与特定组织的再生有关，它们的作用机制是 没有被很好地理解。我们建议继续并完成功能测试，包括生成 果蝇新候选基因的突变。穆恩博士，我们将测试斑马鱼的同源基因. 在研究再生时，必须解决干细胞的问题。TD细胞像干细胞一样分裂吗？ 将在TD细胞中诱导细胞克隆以测定不对称分裂，这是干细胞行为的标志。 然后在存在和不存在表征的增强子的情况下进行这些分析， TD的抑制基因，以测试这些基因是否通过修饰细胞谱系来影响发育可塑性 模式，创始细胞的数量或细胞倍增时间。这项建议将有助于 了解哪些分子信号增加再生潜力，以确保正常组织 维护和修理。 简短摘要 在果蝇的每个成虫盘中有一些特定的细胞具有干细胞的特性。如果受到伤害的挑战 它们会再生我们将测试这些细胞是否不对称分裂，这是干细胞行为的标志。 此外，我们还将鉴定调节发育可塑性的基因，并测试它们的基因产物是如何影响发育的。 影响多能细胞及其周围环境。果蝇一直被用作研究 我们在这里看到了一个深入了解干细胞生物学和再生的机会。