Germ Cell Migration in Drosophila.

果蝇生殖细胞迁移。

基本信息

批准号：
9770562
负责人：
RUTH LEHMANN
金额：
$ 29.66万
依托单位：
NEW YORK UNIVERSITY SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-01 至 2022-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9770562
关键词：
ATP-Binding Cassette Transporters Abdomen Address Adult Affect Afferent Neurons Animals Behavior Behavior Control Biochemical Biological Assay Biological Models Candidate Disease Gene Cartilage Cell Culture Techniques Cell Survival Cell membrane Cell physiology Cells Cellular biology Childhood Complex Cues Destinations Development Drosophila genus Ectopic Expression Embryo Environment Enzymes Face Fibroblasts Genes Genetic Genetic screening method Germ Cells Germ Lines Germinoma Goals Gonadal structure Homologous Gene Human Hydrolysis Hydroxymethylglutaryl-CoA reductase Image Immune system In Vitro Individual Inflammation Knowledge Lipids Location Lymphocyte Mediating Membrane Mesoderm Migration Assay Modeling Modification Morphology Movement Mus Nature Neoplasm Metastasis Neural Crest Cell Neuraxis Organism Ovary Pathway interactions Phospholipids Phosphoric Monoester Hydrolases Phosphotransferases Pigments Play Process RNA RNA Interference Reagent Role Route Signal Pathway Signal Transduction Skin Somatic Cell Structure of primordial sex cell System Systems Analysis Technology Testing Testis Tissues Translating Wound Healing Yeasts Zebrafish base cancer cell cell behavior cell motility cell type egg experimental study extracellular genetic analysis genetic approach in vitro Assay in vivo lipid phosphate phosphatase man migration neoplastic cell neuronal cell body response small hairpin RNA sperm cell tool tumor vertebrate embryos

项目摘要

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. Finally, cells must be able to recognize their target tissue and stop migrating and cells that fail to reach their target have to be eliminated. Primordial germ cells 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. We have used Drosophila to identify signals produced by the soma that guide migrating germ cells. We find that lipid signaling plays a critical role for migrating primordial germ cells. This proposal aims to understand how lipid signaling and membrane composition affect germ cell migration and survival. The aim is to characterize the signaling processes within the germ cells and to determine the nature and distribution of the extracellular signals that guide germ cells. In the first aim we will use a genetic approach targeted at germline expressed genes to identify new and additional components of the migratory machinery in germ cells. In the second aim, we will characterize the lipid targets of the Drosophila lipidphosphate phosphatases, Wunen and Wunen2 that guide germ cells and analyze the nature of the migratory response in germ cells and its role in germ cell survival. In the third aim, we propose to isolate a germ cell attractant produced by the somatic gonad, which we have shown is lipid modified and exported by the somatic gonad cells by an conserved, unconventional ABC transporter. Mis-migration of germ cells in humans is thought to be the cause of germinomas, tumors of the germ line that develop outside of the testis and ovaries. It remains unclear what causes germ cell mis-migration and why these apparently 'lost' germ cells survive outside of the gonad environment. The mechanisms underlying germ cell migration and survival have been studied in genetically tractable organisms such as Drosophila, mouse and zebrafish. These studies have revealed striking parallels in the behavior of germ cells and in the genes that control this behavior. Findings resulting from this application are likely to contribute to a better understanding of the cues and cellular processes that guide germ cell migration and that physically distinguish germ cells from other cells in the body.

描述（由申请人提供）：开发的许多方面都需要单个细胞通过各种和复杂的环境迁移。例如，在脊椎动物胚胎中，神经rest细胞离开发展中心神经系统，并长期迁移，从而引起诸如感觉神经元，面部软骨和色素细胞等细胞类型皮肤。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。在定向细胞迁移期间，运动细胞沿特定路径进行引导，他们识别引导线索并将其转化为有向运动。最后，细胞必须能够识别其目标组织并停止迁移，并且必须消除未能达到目标的细胞。原始生殖细胞为分析定向细胞迁移提供了出色的模型系统。生物细胞生物学的许多方面，例如它们的整体形态和通向性腺躯体成分的好奇迁移路径在整个动物界都保守。我们已经使用果蝇来识别引导生殖细胞迁移的SOMA产生的信号。我们发现脂质信号传导对于迁移原始生殖细胞起着至关重要的作用。这个建议旨在了解脂质信号传导和膜组成如何影响生殖细胞迁移和存活。目的是表征生殖细胞内的信号传导过程，并确定引导生殖细胞的细胞外信号的性质和分布。在第一个目的中，我们将使用针对种系的遗传方法表达基因来识别生殖细胞中迁移机械的新成分和其他组成部分。在第二个目标中，我们将表征果蝇脂磷酸磷酸磷酸酶，Wunen和Wunen2的脂质靶标，这些脂质磷酸酶，Wunen和Wunen2指导生殖细胞并分析生殖细胞中迁移反应的性质及其在生殖细胞存活中的作用。在第三个目标中，我们提出要隔离由体细胞性腺产生的生殖细胞吸引剂，我们所表明的是脂质修饰并由体细胞细胞通过保守的，非常规的ABC转运蛋白进行的。人类中生殖细胞的迁移不良被认为是生殖瘤的原因，睾丸和卵巢以外的生殖系的肿瘤。目前尚不清楚是什么原因导致生殖细胞错误迁移的原因，以及为什么它们显然“丢失”的生殖细胞在性腺环境之外生存。在果蝇，小鼠和斑马鱼等遗传诱导的生物（例如，生殖细胞迁移和生存的机制）已经研究了。这些研究揭示了生殖细胞行为和控制这种行为的基因的惊人相似之处。该应用所产生的发现可能有助于更好地理解引导生殖细胞迁移并物理区分生殖细胞与体内其他细胞的细胞过程。