Germ Cell Migration in Drosophila

描述(由申请人提供)：发育的许多方面需要单个细胞在不同和复杂的环境中迁移。在……里面 例如，脊椎动物的胚胎，神经脊细胞离开了发育阶段 中枢神经系统和长距离迁徙产生这样的 细胞类型包括感觉神经元、面部软骨和皮肤色素细胞。 在成年人中，迁移细胞类型包括免疫系统的细胞， 伤口愈合过程中的成纤维细胞，以及转移过程中的癌细胞。在.期间 定向的细胞迁移，可移动的细胞沿着特定的路径被引导，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 定向的细胞迁移。生殖细胞生物学的许多方面，例如他们的 整体形态及其向体细胞的奇怪迁徙路径 性腺的组成部分在整个动物界都是保守的。排斥力 来自中肠后部和对体细胞性腺前体的吸引 在果蝇体内定位生殖细胞的迁移。引导性导引 提示由果蝇HMGCoA还原酶提供。高水平的HMGCoA还原酶 都是将原生殖细胞吸引到体细胞性腺的必要条件和充分条件。一个 驱避剂引导信号由两个冗余作用的蛋白质Wunen提供 和武能2号，表达在中肠上。异位武能/武能2 表达排斥生殖细胞，高水平表达会导致PGC死亡。本研究 建议描述这些令人厌恶和吸引人的信号系统 使用遗传和生化来确定各自信号的性质 技巧。本研究进一步旨在确定该病毒的分子性质。 生殖细胞中介导迁移反应的受体。给定 保护动物的发育机制很可能是 研究生殖细胞导向的分子机制将有助于 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.