Genetic Control of Intestinal Stem Cells in the Drosophila Hindgut

大多数成人器官含有缓慢循环的未分化干细胞群体。 除了维持自身数量外，干细胞还能产生分化的后代， 转化为它们所在器官的各种细胞类型。成体干细胞在 深入研究的目的是将这些细胞用于再生医学。 此外，已经清楚的是，肿瘤生长通常从茎开始， 细胞或其增殖后代。一个重要的成体干细胞群体是 肠上皮干细胞。我们最近在果蝇成虫中发现 后肠是一种与哺乳动物高度相似的干细胞系统， 肠道干细胞，但同时也更容易进行基因分析， 和发展。果蝇后肠干细胞仅限于一小段 后肠，后肠增殖区（HPZ）。在HPZ内，自我更新， 增殖和分化由四种信号传导途径的局部来源控制， Wnt/Wingless、Hedgehog、Notch和Jak/Stat途径。在项目中，我们 将解决HPZ的一些基本属性：什么是功能 这些途径之间的关系，以及干细胞行为（细胞 循环？附着力？迁移？多能性？）每个人都控制？此外，委员会认为， 果蝇肠道的快速发育和相对简单， 有机会调查何时以及如何利用HPZ的特殊信号特性 在发展过程中。最后，我们想筛选与成体干细胞相关的新基因， 细胞增殖我们的总体目标是将飞行HPZ系统的知识提高到 程度，使其能够制定额外的，具体的和易于翻译 研究计划，使用苍蝇后肠干细胞作为模型系统。

Most adult organs contain populations of slowly cycling, undifferentiated stem cells. Aside from maintaining their own numbers, stem cells produce progeny that differentiate into the various cell types of the organ they are located in. Adult stem cells are under intensive study with the goal in mind to use these cells in regenerative medicine. Furthermore, it has become clear that neoplastic growth typically takes off from stem cells or their proliferating progeny. One important population of adult stem cells are the epithelial stem cells of the intestine. We recently found in the Drosophila adult hindgut a stem cell system that shows a high degree of similarity to the mammalian intestinal stem cells, but at the same time is considerably simpler to analyze genetically and developmentally. Drosophila hindgut stem cells are confined to a short segment of the hindgut, the hindgut proliferation zone (HPZ). Within the HPZ, self renewal, proliferation and differentiation is controlled by local sources of four signaling pathways, the Wnt/Wingless, Hedgehog, Notch and Jak/Stat pathway. In the proposed project we will address some fundamental properties of the HPZ: what are the functional relationships between these pathways, and what aspect of stem cell behavior (cell cycle? adhesion? migration? pluripotency?) does each of them control? Furthermore, the rapid development and relative simplicity of the Drosophila intestinal tract gives us the opportunity to investigate when and how the HPZ with its special signaling properties during development. Finally, we want to screen for novel genes involved in adult stem cell proliferation. Our overall goal is to advance the knowledge of the fly HPZ system to a degree that makes it possible to formulate additional, specific and readily translatable research programs, using the fly hindgut stem cells as a model system.