Zinc Regulation of Germline and Embryo Development in Caenorhabditis elegans

锌对秀丽隐杆线虫种系和胚胎发育的调节

• 批准号: 8786354
• 负责人: Adelita D. Mendoza
• 金额: $ 3.6万
• 依托单位: NORTHWESTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8786354
• 关键词: Adult; Affect; Area; Binding; Binding Proteins; Biological Sciences; Biology; Caenorhabditis elegans; Calcium; Cell Cycle; Cell Cycle Progression; Cell Cycle Regulation; Cell division; Cell physiology; Cells; Chromosome abnormality; Collaborations; Cyclin E; Development; Embryo; Embryonic Development; Environment; Event; Fluorescent Dyes; Germ Cells; Goals; Gonadal structure; Health; Histocompatibility Testing; Homeostasis; Human; Image; Invertebrates; Knowledge; Laboratories; Lead; Longevity; Mammals; Meiosis; Messenger RNA; Methods; Mitosis; Mitotic; Molecular; Morphology; Mus; Nature; Notch Signaling Pathway; Oocytes; Pathway interactions; Phosphorus; Photons; Play; Process; Proteins; Proxy; Regulation; Research; Role; Signal Pathway; Signal Transduction; Source; Structure; Testing; Time; Transition Elements; Universities; Work; Zinc; Zinc Fingers; anaphase-promoting complex; cell growth regulation; cofactor; human disease; in vivo; inhibitor/antagonist; interdisciplinary approach; knowledge base; notch protein; novel; offspring; physical science; public health relevance; reproductive; reproductive development; research study; sperm cell

DESCRIPTION (provided by applicant): Zinc is a transition metal that plays a role in an array of cellular processes and has traditionally been considered a cofactor and structural regulator. We propose a novel and unprecedented role for zinc as regulator in inorganic cell signaling. Studies from the O'Halloran and Woodruff labs have demonstrated that zinc regulates meiotic progression in mouse oocytes through massive zinc fluxes and association of zinc with the zinc-finger binding protein Emi2. The discovery that zinc is a master regulator of cell cycle progression has the potential to broadly impact the study of human disease, as extreme levels of zinc present in our cells can negatively affect cell division. We are expanding studies into Caenorhabditis elegans, to exploit their short reproductive lifespan, high number of offspring and translucence. It is unknown if zinc master regulation is a conserved cell signaling mechanism in C. elegans. Therefore, the proposed aims will fill this knowledge gap and identify how the zinc regulated cell signaling pathway defines the developing germline. We will achieve this goal by quantifying total and labile zinc within the gonad, test mechanisms of zinc switching events to define different regions of the gonad and identify the molecular mechanism of master zinc regulation of the Notch signaling pathway. These experiments will be conducted under zinc deficient conditions compared to controls. Information acquired from these studies will advance the knowledge base in zinc as a cell signaling regulator and lead to further understanding how zinc regulates cell cycle and thus germ cell identity, which is crucial for the development of new offspring.

描述（由申请人提供）：锌是一种过渡金属，在一系列细胞过程中起作用，传统上被认为是辅因子和结构调节剂。我们提出了锌作为无机细胞信号传导中的调节剂的新颖和前所未有的作用。来自O'Halloran和Woodruff Labs的研究表明，锌通过巨大的锌通量调节小鼠卵母细胞的减数分裂进程，以及锌与锌指结合蛋白EMI2的关联。发现锌是细胞周期进程的主要调节剂的发现有可能广泛影响人类疾病的研究，因为我们细胞中存在的极端水平会对细胞分裂产生负面影响。我们正在将研究扩展到秀丽隐杆线虫，以利用其短期生殖寿命，大量后代和半透明。尚不清楚锌主调节是否是秀丽隐杆线虫中保守的细胞信号传导机制。因此，拟议的目标将填补这一知识差距，并确定锌调节的细胞信号通路如何定义发育型种系。我们将通过量化性腺内的总和不稳定的锌来实现这一目标，即锌开关事件的测试机制来定义性腺的不同区域，并确定Notch信号通路的主锌调节的分子机制。与对照组相比，这些实验将在锌不足条件下进行。从这些研究中获取的信息将作为细胞信号调节剂中的锌的知识库提高知识基础，并进一步了解锌如何调节细胞周期，从而调节生殖细胞身份，这对于新后代的发展至关重要。