Collaborative Research: RUI: Regulating the Tribolium segmentation clock

动物的身体是由重复的部分组成的——被称为节段——就物种的绝对数量而言，它们主宰着地球。无论是昆虫还是鱼类，这种广泛的身体计划在进化过程中都是非常成功的。有一个分段的身体需要一种在身体计划发展的早期阶段产生重复片段的方法。最近的研究表明，非常不同类型的动物可能都使用某种遗传时钟，将时间上重复的振荡转化为空间上重复的片段。最著名的“分割时钟”来自对脊椎动物的研究。但是，这种时钟是否以及如何在地球上最多样化的动物群体——节肢动物——中起作用，目前的研究还相对不足。本项目以一种节肢动物——面粉甲虫为研究对象，探索驱动其“分割时钟”的基因。这种关注源于先前的工作，表明生物钟在发育过程中改变了它制造片段的速度。最终了解分段的身体是如何构建的，可以深入了解人类发展过程中沿身体轴出现的问题。这项工作是一项合作努力，将教学学院的本科生与研究型大学的科学家联系起来，充分利用大学的资源。增加教学学院本科生接触不同和更多样化的研究技术的机会，可以增加他们在科学事业方面的训练和准备。由重复的节段构成的动物分为三个主要分类群。脊椎动物使用一种类似“时钟”的机制来按顺序排列它们的节段。最近，在节肢动物——面粉甲虫（Tribolium castaneum）身上发现了第一个明确的分割时钟。目前的Tribolium时钟模型与更知名的脊椎动物模型有着有趣的不同。这个项目主要关注Tribolium时钟的三个关键特征。首先，Tribolium时钟在原肠胚的细胞运动之前就开始形成模式，这就提出了一个问题，即在细胞广泛运动期间如何维持时钟输出。其次，以往的研究表明，在分割的早期和后期，时钟频率和细胞运动都发生了变化。这些变化是如何调节和相互协调的？第三，没有发现细胞间信号通路来协调细胞间的时钟，这一结果得到了初步计算模型的支持。生物钟能细胞自主运作吗？本研究旨在通过生成囊胚的全面命运图来研究Tribolium分割时钟，并确定时钟调节因子在原肠胚早期过渡时期的表达稳定性。它还旨在通过将经典启动子解剖与生物信息学和高通量基因组学方法相结合，通过时钟的不同阶段发现新的分子调节因子。

Animals whose bodies are built from repeated parts - called segments - dominate the planet in terms of sheer numbers of species. This widespread body plan, whether in groups like insects or fish, has been highly successful during the course of evolution. Having a segmented body requires a means of producing repeated segments during the early life stages in which the body plan develops. Recent work has shown that very different types of animals may all use some kind of genetic clock that translates temporally repeated oscillations into spatially repeated segments. The best known "segmentation clock" is from studies in vertebrate animals. But if, and how, such a clock operates in the most diverse group of animals on earth, the arthropods, remains relatively understudied. This project focuses on one arthropod, the flour beetle, and explores the genes driving its "segmentation clock". This focus arises from previous work showing that the clock changes the rate at which it makes segments midway through development. Ultimately understanding how segmented bodies are built can provide insight into how problems arise along the body axis during human development. This work is a collaborative effort that links undergraduates from a teaching college to scientists at a research university, leveraging the resources of the university. Increasing the exposure of undergraduates at the teaching college to both different and more varied research technologies increases their training and preparation for careers in science.Animals built from repeated segments are found in three major taxa. Vertebrates use a "clock"-like mechanism to sequentially pattern their segments. Recently the first unequivocal segmentation clock has been demonstrated in an arthropod: the flour beetle, Tribolium castaneum. The current model of the Tribolium clock differs in intriguing ways from the better-known vertebrate models. This project focuses on three key features of the Tribolium clock. First, the Tribolium clock begins patterning before the cell movements of gastrulation, raising the question of how clock outputs are maintained during extensive cell movements. Second, previous research showed that both the clock frequency and cell motility change between early and late segmentation. How are these changes regulated and mutually coordinated? Third, no intercellular signaling pathways have been identified to coordinate the clock between cells, a result supported by a preliminary computational model. Can the clock function cell-autonomously? This research aims to examine the Tribolium segmentation clock by generating a comprehensive fate map of the blastoderm, and determining the stability in expression of clock regulators during the early transition of gastrulation. It also aims to uncover novel molecular regulators through different phases of the clock, by combining classical promoter dissection with bioinformatics and high-throughput genomics approaches.