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

超出所提供的空间。组织是由干细胞形成和维持的，干细胞既能产生进行自我更新增殖的子细胞，也能产生分化的子细胞。在任何系统中，在增殖和分化之间作出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秀丽隐杆线虫生殖系中增殖与分化的决定是如何做出的。GLP-1 /Notch信号通路诱导生殖细胞增殖，而GLD-1是一种保守的翻译抑制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线虫增殖和减数分裂发育之间的正确平衡。哺乳动物的Notch信号在干细胞自我更新和致癌Notch激活中也很重要。Aim 1的目标是鉴定和表征GLP-1/Notch信号的负调控因子，其功能是限制增殖性生殖细胞群的大小。Notch信号下调的机制尚不清楚，但具有普遍重要性，因为在许多发育环境中，激活的Notch蛋白必须在连续几轮Notch介导的细胞命运规范（例如神经系统）之间被清除。Aim 2采用细胞生物学方法了解GLP-1/Notch信号如何控制20个细胞直径范围内的增殖。GLD-1水平的升高是由翻译激活因子和翻译抑制因子共同调控的，它决定了生殖细胞进入减数分裂的位置，在Aim 3中，这种控制所需的额外基因产物将被识别和表征。在Aim 4中，GLD-1介导减数分裂发育起始的mRNA靶点将被识别和表征。GLD-1可能通过翻译抑制这些rna来促进减数分裂发育。由于对导致动物进入减数分裂前期的活动知之甚少，因此该目标的结果将提供一个初步的图像。网站性能 ======================================== 节结束 ===========================================

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===========================================