Germ Cell Migration in Drosophila

描述（由申请人提供）：开发的许多方面需要 单个细胞在复杂多样的环境中迁移。在 脊椎动物胚胎，例如，神经嵴细胞离开发育中的 中枢神经系统，并迁移到长距离，以产生这种 细胞类型如感觉神经元、面部软骨和皮肤色素细胞。 在成人中，迁移细胞类型包括免疫系统的细胞， 伤口愈合期间的成纤维细胞和转移期间的癌细胞。期间 定向细胞迁移，运动细胞被引导沿着特定的路径，它们 识别引导线索并将其转化为定向运动。 原始生殖细胞（PGCs）为分析提供了一个很好的模型系统 定向细胞迁移的机制生殖细胞生物学的许多方面，例如它们的 整体形态和他们好奇的迁移路径向躯体 生殖腺的组成部分在整个动物界都是保守的。排斥 从后中肠和吸引向体细胞性腺前体 在果蝇的生殖细胞迁移过程中定向。一种引诱剂引导 提示由果蝇HMGCoA还原酶提供。高水平HMGCoA还原酶 是将PGCs吸引到体细胞性腺的必要条件和充分条件。一 排斥性引导信号由两个冗余作用蛋白质提供，Wunen 和Wunen 2，它们在中肠上表达。异位Wunen/Wunen 2 表达排斥生殖细胞，并且在高水平时导致PGC死亡。本研究 提出了这些排斥和吸引信号系统的特点， 使用遗传和生物化学方法来确定各个信号的性质 技术.本研究进一步旨在确定 生殖细胞中介导迁移反应的受体。鉴于 保护动物的发育机制很可能是， 对生殖细胞引导的分子机制的研究将有助于 生殖细胞迁移的一般分析。

DESCRIPTION (provided by applicant): Many aspects of development require the migration of individual cells through diverse and complex environments. In vertebrate embryos, for example, neural crest cells leave the developing central nervous system and migrate over long distances to give rise to such cell types as sensory neurons, facial cartilage and pigment cells of the skin. In adults, migratory cell types include the cells of the immune system, fibroblasts during wound healing, and cancer cells during metastasis. During directed cell migration, motile cells are guided along a particular path, they recognize guidance cues and translate them into directed movement. Primordial germ cells (PGCs) provide an excellent model system for the analysis of directed cell migration. Many aspects of germ cell biology, such as their overall morphology and their curious migratory path toward the somatic components of the gonad are conserved throughout the animal kingdom. Repulsion from the posterior midgut and attraction toward the somatic gonadal precursors orients germ cells during their migration in Drosophila. An attractant guidance cue is provided by Drosophila HMGCoA reductase. High levels of HMGCoA reductase are both necessary and sufficient to attract PGCs to the somatic gonad. A repellant guidance cue is provided by two redundantly acting proteins, Wunen and Wunen 2, which are expressed on the midgut. Ectopic Wunen/Wunen 2 expression repels germ cells and at high levels leads to PGC death. This study proposes to characterize these repellant and attractive signaling systems and to determine the nature of the respective signals using genetic and biochemical techniques. This study further aims to determine the molecular nature of receptors in the germ cells that mediate the migratory response. Given the conservation of developmental mechanisms among animals it is likely that studies on the molecular mechanisms of germ cells guidance will contribute to the analysis of germ cell migration in general.