GLD-1 CONTROL OF MEIOSIS AND GAMETOGENESIS IN C. ELEGANS

GLD-1 对线虫减数分裂和配子发生的控制

• 批准号: 7018725
• 负责人: TIM SCHEDL
• 金额: $ 12.5万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1979
• 资助国家: 美国
• 起止时间: 1979-04-01 至 2005-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7018725
• 关键词: GLD; CONTROL; MEIOSIS; GAMETOGENESIS; C.

EXCEED THE SPACE PROVIDED. Tissues are formed and maintained by stem cells that produce both daughters that undergo self-renewing proliferation and daughters that differentiate. The mechanisms by which the choice between proliferation and differentiation are made are not well understood in any system. Our long-term goal is to understand how the proliferation vs. differentiation decision is made in the C. elegans germline. The GLP-1 /Notch signaling pathway induces germ cells to proliferate while GLD-1, a conserved translational represser RNA binding protein, is a key downstream differentiation factor that promotes meiotic development. Spatial control of both GLP-1/Notch signaling and GLD-1 accumulation determines the correct balance between proliferation and meiotic development in C. elegans. Notch signaling in mammals is also important in stem cell self-renewal and oncogenic Notch activation can lead to cancer. The goal of Aim 1 is to identify and characterize negative regulators of GLP-1/Notch signaling that function to limit the size of the proliferative germ cell population. Mechanisms by which Notch signaling is down-regulated are not well understood but are of general importance since there are a number of developmental contexts where activated Notch proteins must be cleared between successive rounds of Notch mediated cell fate specification (e.g. nervous system). Aim 2 employs cell biological approaches to understand how GLP-1/Notch signaling controls proliferation over a distance of 20 cell diameters. The rise in GLD-1 levels, which is regulated by both translational activators and repressers, determines where germ cells enter meiosis and in Aim 3, additional gene products necessary for this control will be identified and characterized. In Aim 4, mRNA targets of GLD-1 that mediate initiation of meiotic development will be identified and characterized. GLD-1 likely translationally represses these RNAs to promote meiotic development. Since little is known about activities that lead to entry into meiotic prophase in animals, results from this aim will provide an initial picture. PERFORMANCE SITE ========================================Section End===========================================

超出所提供的空间。组织由干细胞形成和维持，干细胞产生经历自我更新增殖的子细胞和分化的子细胞。在任何系统中，在增殖和分化之间进行选择的机制都没有得到很好的理解。我们的长期目标是了解C.秀丽隐杆线虫生殖系GLP-1 /Notch信号通路诱导生殖细胞增殖，而GLD-1是一种保守的翻译阻遏RNA结合蛋白，是促进减数分裂发育的关键下游分化因子。GLP-1/Notch信号和GLD-1积累的空间控制决定了C.优雅的哺乳动物中的Notch信号传导在干细胞自我更新中也是重要的，并且致癌Notch激活可导致癌症。目的1的目的是鉴定和表征GLP-1/Notch信号传导的负调节因子，其功能是限制增殖生殖细胞群的大小。Notch信号传导被下调的机制尚未被很好地理解，但具有普遍重要性，因为存在许多发育环境，其中活化的Notch蛋白必须在连续轮的Notch介导的细胞命运特化（例如神经系统）之间被清除。目的2采用细胞生物学方法来了解GLP-1/Notch信号传导如何控制20个细胞直径的距离上的增殖。GLD-1水平的升高受翻译激活因子和阻遏因子的调节，决定了生殖细胞进入减数分裂的位置，在目标3中，将鉴定和表征这种控制所需的其他基因产物。在目标4中，将鉴定和表征介导减数分裂发育起始的GLD-1的mRNA靶点。GLD-1可能抑制这些RNA以促进减数分裂发育。由于对动物进入减数分裂前期的活动知之甚少，因此这一目标的结果将提供一个初步的图景。性能现场=