Collaborative Research: Regulating the Tribolium segmentation clock

合作研究：调节Tribolium分段时钟

• 批准号: 1755188
• 负责人: Lisa Nagy
• 金额: $ 60万
• 依托单位: University of Arizona
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-01-15 至 2022-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1755188&HistoricalAwards=false
• 关键词: Collaborative; Research; Regulating; Tribolium; segmentation

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.

动物的身体由重复的部分组成--被称为节段--就物种的绝对数量而言，它们主导着地球。这种广泛的身体计划，无论是以昆虫或鱼类为群体，在进化过程中都非常成功。拥有一个分段的身体需要一种在身体计划制定的早期生命阶段产生重复分段的手段。最近的研究表明，非常不同类型的动物都可能使用某种遗传时钟，这种时钟将时间上重复的振荡转化为空间上重复的片段。最广为人知的“分段时钟”来自对脊椎动物的研究。但是，这样的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--中运行，仍然相对缺乏研究。该项目以一种节肢动物--面粉甲虫为研究对象，探索驱动其“分段时钟”的基因。这一重点源于之前的工作，该工作表明，时钟在发育中途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，可以深入了解在人类发育过程中，身体轴上的问题是如何出现的。这项工作是一项合作努力，将师范学院的本科生与研究型大学的科学家联系起来，利用大学的资源。增加师范学院本科生对不同和更多样化的研究技术的接触，会增加他们在科学领域的培训和准备。由重复片段组成的动物存在于三个主要的分类群中。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，第一个明确的分段时钟在节肢动物中被证明：面粉甲虫，卡氏拟谷盗。目前的Tribolium时钟模型与更知名的脊椎动物模型有有趣的不同之处。该项目重点介绍Tribolium时钟的三个关键特性。首先，Tribolium时钟在原肠形成的细胞运动之前就开始构图，这提出了一个问题，即在广泛的细胞运动期间如何保持时钟输出。其次，先前的研究表明，时钟频率和细胞运动性在早期和晚期的分割之间都发生了变化。这些变化是如何监管和相互协调的？第三，还没有发现协调细胞间时钟的细胞间信号通路，这一结果得到了初步计算模型的支持。这个时钟能在细胞内自主工作吗？本研究旨在通过生成胚胚层的全面命运图，并确定原肠胚早期转换过程中时钟调节因子表达的稳定性，来检测Tribolium的分裂时钟。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控因子。