Post-transcriptional control of Lunatic fringe in the segmentation clock

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。在胚胎发生过程中，精子和卵细胞融合产生的单细胞发育成一个复杂的多细胞生物。为了使这一过程正常进行，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。本研究探讨了胚胎发生过程中用于记录脊柱和肋骨发育过程的遗传“时钟”（称为分割时钟）的功能和机制。参与这个时钟的基因之间的相互作用有点像机械时钟中的齿轮，每个基因的振荡影响其他基因的功能。先前的研究表明，扰乱生物钟相关基因功能的基因突变会影响胚胎发育，导致脊柱和肋骨发育异常。这里提出的工作检查了在发育过程中控制时钟-基因活动的机制，本质上决定了时钟中遗传“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相关基因活性的遗传和生化机制来完成。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，并使我们了解胚胎在关键解剖结构发育过程中如何控制时间调节事件。这项研究还将支持研究生和本科生的教育，使发展中的科学家能够将研究原则融入他们的教育中。

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.