Regeneration of Imaginal Discs in Drosophila

果蝇成虫盘能够再生，从而为我们提供了一个研究模型系统 细胞的多能性。在某些条件下，每个成虫盘的“弱点”中都有一小群细胞 改变他们的命运。这种转换称为转决定 (TD)，当 wg 为 过度表达或当光盘被切入“薄弱点”时。鉴定出这些细胞的表达谱 在功能测试中显着改变 TD 的候选基因。其中一些候选人是 染色质重塑基因。此外，我们还鉴定了假定的再生基因，例如air-like、a 与小鼠肝再生基因增强剂（空气）同源的基因，基质金属蛋白酶 1 (Mmp1) 和 dReg，一种包含 C-凝集素结构域的新基因，虽然哺乳动物的直系同源物 这三个基因与特定组织的再生有关，它们作用的机制是 不太理解。我们建议继续并完成功能测试，包括生成 新候选果蝇基因的突变。 Moon博士，我们将测试同源斑马鱼基因。 在检查再生时，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来检测不对称分裂，这是干细胞行为的一个里程碑。 然后将在存在和不存在特征增强子的情况下进行这些分析 TD 抑制因子来测试这些基因是否通过改变细胞谱系影响发育可塑性 模式、创始细胞数量或细胞倍增时间。该提案将有助于 了解哪些分子信号可增加再生潜力以确保组织正常 保养和维修。 简短摘要 果蝇每个成虫盘中的一些特定细胞具有干细胞特性。如果受到伤害挑战 他们重生了。我们将测试这些细胞是否不对称分裂，这是干细胞行为的一个里程碑。 此外，我们将鉴定介导发育可塑性的基因，并测试它们的基因如何产生 影响多能细胞及其周围环境。果蝇已被用作模型系统来研究 人类疾病，我们在这里看到了深入了解干细胞生物学和再生的机会。

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.