Molecular mechanisms of oocyte development in Drosophila

果蝇卵母细胞发育的分子机制

基本信息

批准号：
10793787
负责人：
Elizabeth Tweedie Ables
金额：
$ 45.3万
依托单位：
EAST CAROLINA UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-01-01 至 2026-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10793787
关键词：
Adult Biological Assay Biological Models Biomedical Research Bone Morphogenetic Proteins Cell Cycle Progression Cell Maintenance Cell physiology Cells Complex Cues Cyst DNA Binding Data Development Diet Drosophila genus Ecdysone Enhancers Environment Estrogen Receptors Event Experimental Designs Experimental Models Female Fertility Funding Generations Genes Genetic Genetic Models Genetic Transcription Germ Cells Germ cell tumor Goals Gonadal structure Growth Hormonal Hormones Human Immunofluorescence Immunologic Infrastructure Invertebrates Knowledge Link Maintenance Mediator Mentors Modeling Molecular Monitor Movement Nuclear Receptors Nucleic Acid Regulatory Sequences Nutrient Nutritional Oocytes Oogenesis Ovarian Ovary Process Production Productivity Proliferating Quantitative Reverse Transcriptase PCR RNA RXR Reagent Regulator Genes Reporter Research Research Training Resources Retinoic Acid Receptor Role Rural Signal Induction Signal Pathway Signal Transduction Signaling Protein Somatic Cell Steroids Students Testing Time Training Transcriptional Regulation Transgenes Undifferentiated Universities cell cortex dietary ecdysone receptor experience experimental study gain of function genome-wide germline stem cells hormonal signals imaging approach in vivo in vivo evaluation laboratory experience live cell imaging loss of function mother nutrition novel nutrition offspring oocyte quality overexpression receptor response self-renewal stem cells stem-like cell steroid hormone tool transcriptome transcriptomics undergraduate research undergraduate student

项目摘要

PROJECT SUMMARY/ABSTRACT Successful gamete production and survival of offspring in humans and invertebrates depends on optimal nutrition. The molecular mechanisms connecting gamete production with nutritional cues, however, remain unclear. Steroid hormones, via specific nuclear receptors, are diet-induced signals that promote germ cell development. Our long-term goal is to characterize how ovarian cells respond to steroid hormone signaling. Our undergraduate-powered research team uses the genetically tractable Drosophila ovary to monitor germ cell development in vivo in response to dietary and hormonal cues. The steroid hormone ecdysone has long been recognized for its role in oocyte development. Previous studies, however, have been unable to disentangle the multitude of effects of the steroid hormone, precluding identification of relevant molecular mechanisms. Our lab has developed novel reagents to specifically isolate germ cell autonomous reception of ecdysone signaling independent of its other roles. Building on our previous studies, our team of undergraduates and Master's students will test the hypothesis that ecdysone signaling through the receptor EcR autonomously in germ cells promotes an undifferentiated germ cell fate in germline stem cells, and follicle assembly in differentiated germ cells. In Aims 1 and 2, we will use sophisticated genetic tools, cell signaling reporters, and transcriptomics, and novel transcriptional enhancers to determine the transcriptional response to EcR in undifferentiated germ cells. In Aim 3, we will use gain and loss of function approaches combined with live cell imaging to test in vivo how EcR in germ cells promotes follicle formation. Results from these experiments will further our understanding of the molecular mechanisms by which steroid signaling promotes oocyte growth and survival, which have long been under-explored. Furthermore, this proposal will continue to support infrastructure at a large, regional, rural, public university, using a very approachable model system to provide high-impact biomedical research experiences to underserved undergraduates in a supportive training environment.

项目概要/摘要人类和无脊椎动物的配子成功产生和后代的存活取决于最佳配子营养。然而，将配子产生与营养线索联系起来的分子机制仍然存在不清楚。类固醇激素通过特定的核受体，是饮食诱导的促进生殖细胞的信号发展。我们的长期目标是表征卵巢细胞如何响应类固醇激素信号。我们的由本科生支持的研究小组使用遗传易处理的果蝇卵巢来监测生殖细胞体内发育响应饮食和激素线索。类固醇激素蜕皮激素长期以来因其在卵母细胞发育中的作用而得到认可。然而，之前的研究未能理清这一问题类固醇激素的多种作用，排除了相关分子机制的鉴定。我们的实验室开发了新的试剂来特异性分离生殖细胞自主接收蜕皮激素信号独立于其其他角色。基于我们之前的研究，我们的本科生和硕士团队学生将测试生殖细胞中蜕皮激素通过受体 EcR 自主发出信号的假设促进生殖系干细胞中未分化生殖细胞的命运，以及分化生殖细胞中卵泡的组装细胞。在目标 1 和 2 中，我们将使用复杂的遗传工具、细胞信号报告基因和转录组学，以及新型转录增强子，用于确定未分化生殖细胞中对 EcR 的转录反应。在目标 3 中，我们将使用功能获得和丧失的方法结合活细胞成像来测试体内如何生殖细胞中的 EcR 促进卵泡形成。这些实验的结果将进一步加深我们的理解类固醇信号传导促进卵母细胞生长和存活的分子机制，长期以来一直存在尚未得到充分探索。此外，该提案将继续支持大型、区域、农村、公立大学，使用非常平易近人的模型系统来提供高影响力的生物医学研究在支持性培训环境中为服务不足的本科生提供经验。