Post-transcriptional control of Lunatic fringe in the segmentation clock

点击翻译按钮获取中文摘要

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.