Post-transcriptional control of Lunatic fringe in the segmentation clock

分段时钟中 Lunatic 条纹的转录后控制

• 批准号: 0919649
• 负责人: Susan Cole
• 金额: $ 68.5万
• 依托单位: Ohio State University Research Foundation -DO NOT USE
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-15 至 2013-09-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0919649&HistoricalAwards=false
• 关键词: Post; transcriptional; control; Lunatic; fringe

This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5).During embryogenesis, the single cell produced upon fusion of the sperm and egg cells develops into a complex, multicellular organism. For this process to occur properly, the developing embryo must turn genes on and off in distinct cells at the right times and in the correct sequential order. The research proposed here investigates the function and mechanism underlying a genetic "clock" (called the segmentation clock) that is utilized during embryogenesis to time processes involved in the development of the spine and ribs. The genes involved in this clock interact somewhat like gears in a mechanical clock, with the oscillations of each individual gene affecting the function of others. Previous work has shown that genetic mutations that perturb clock-linked gene function affect embryonic development, resulting in abnormal development of the spine and ribs. The work proposed here examines the mechanisms that control clock-gene activity during development, essentially determining how the sizes of the genetic "gears" or "gear ratios" in the clock are regulated. This will be accomplished by examining the genetic and biochemical mechanisms that control clock-linked gene activity at the level of RNA and protein function. These experiments are expected to enhance our understanding of the segmentation clock, elucidating mechanisms that control the function of a critical cell to cell communication pathway in the clock, and informing our understanding of how embryos control time-regulated events during development of key anatomical structures. This research will also support the education of graduate and undergraduate students, allowing developing scientists to integrate principles of research into their education.

该奖项是根据2009年美国复苏和再投资法案（公法111-5）资助的。在胚胎发育过程中，精子和卵细胞融合后产生的单细胞发育成复杂的多细胞生物体。为了使这一过程正确发生，发育中的胚胎必须在正确的时间和正确的顺序打开和关闭不同细胞中的基因。这里提出的研究调查了遗传“时钟”（称为分割时钟）的功能和机制，该时钟在胚胎发育过程中用于脊柱和肋骨发育的时间过程。参与这个时钟的基因相互作用有点像机械时钟中的齿轮，每个基因的振荡都会影响其他基因的功能。先前的研究表明，扰乱时钟连锁基因功能的基因突变会影响胚胎发育，导致脊柱和肋骨的异常发育。这里提出的工作研究了在发育过程中控制时钟基因活动的机制，基本上确定了时钟中遗传“齿轮”或“齿轮比”的大小是如何调节的。这将通过检查在RNA和蛋白质功能水平上控制时钟连锁基因活性的遗传和生化机制来实现。这些实验有望增强我们对分割时钟的理解，阐明控制时钟中关键细胞间通信途径功能的机制，并告知我们胚胎如何在关键解剖结构发育过程中控制时间调节事件的理解。这项研究还将支持研究生和本科生的教育，使发展中的科学家将研究原则融入他们的教育。