Germ Cell Migration in Drosophila

果蝇生殖细胞迁移

• 批准号: 6642014
• 负责人: RUTH LEHMANN
• 金额: $ 34.39万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-01 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6642014
• 关键词: Drosophilidae; G protein; HMG coA reductases; alleles; biological signal transduction; cell migration; gene expression; genetic screening; germ cells; mesoderm; method development; phospholipids; protein sequence; protein structure function; receptor coupling; tissue /cell culture

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.

描述（由申请人提供）：发育的许多方面都需要单个细胞在多样化和复杂的环境中迁移。在 脊椎动物胚胎，例如，神经嵴细胞离开发育 中枢神经系统并长距离迁移以产生这种 细胞类型为感觉神经元、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 (PGC) 为分析提供了出色的模型系统 细胞定向迁移。生殖细胞生物学的许多方面，例如它们的 整体形态和它们奇怪的体细胞迁移路径 性腺的组成部分在整个动物界中得到保留。斥力 来自后中肠和对体细胞性腺前体的吸引力 在果蝇中生殖细胞迁移过程中定向。引诱性引导 提示由果蝇 HMGCoA 还原酶提供。高水平的 HMGCoA 还原酶 对于吸引 PGC 到体细胞性腺来说既是必要的又是充分的。一个 驱避引导信号由两种冗余作用蛋白 Wunen 提供 和 Wunen 2，在中肠上表达。异位Wunen/Wunen 2 表达会排斥生殖细胞，高水平会导致 PGC 死亡。这项研究 提出描述这些令人厌恶和有吸引力的信号系统的特征， 使用遗传和生化确定各个信号的性质 技术。这项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 动物之间发育机制的保护很可能 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。