Investigating the gene regulatory network underlying the segmentation clock of the flour beetle Tribolium castaneum

这项研究将确定重要的相似性和差异的方式不同的节肢动物（即果蝇，甲虫和蜘蛛）和脊椎动物（即鱼，小鼠和人类）在胚胎发育过程中发展自己的身体。这项工作对于了解形成动物身体计划的遗传和发育机制如何随着进化时间的推移而变化和分化，以产生我们今天在自然界中看到的不同类型的动物身体计划至关重要。这对于理解所有动物的共同祖先如何在5.5亿年前的进化历史中发展其身体计划也很重要。人类和其他脊椎动物拥有分段的身体计划：我们身体的内部部分被分成独立和重复的结构，例如我们的椎骨和肋骨。脊椎动物胚胎在发育过程中生长，头部结构首先形成，躯干按从前到后的顺序生长。在这个过程中，细胞群，后来会产生肋骨/椎骨是确定早期，一个接一个，在前到后的顺序。这个过程由基因网络控制，这些基因网络反复打开和关闭以定义每组细胞（即每个未来的肋骨/椎骨）。这种复杂的基因振荡网络被称为脊椎动物分割时钟。节肢动物，包括果蝇，甲虫和蜘蛛，也有明显的分段身体计划。赤拟谷盗的腹部体节在甲虫发育过程中以从前到后的顺序一个接一个地形成，其过程类似于上文对脊椎动物所述的过程。我最近表明，这一发展过程也是由一个基因网络控制的，该网络振荡以顺序模式腹部节-节肢动物分割时钟。有趣的是，果蝇（Drosophila melanogaster）的进化加快了其发育速度，使得所有身体部分在卵中同时形成，这一过程已经被生物学家在遗传水平上很好地理解。这项工作计划的第一个目标是确定节肢动物分割时钟背后的基因网络是否以类似于脊椎动物分割时钟的方式组织。如果发现惊人的相似之处，这可能表明分割时钟是节肢动物和脊椎动物共同祖先的一个特征。或者，如果存在显著的差异，这可能表明不同的动物群体独立且平行地进化出了相似的遗传机制。无论哪种方式，这项研究有望揭示我们的进化history.The第二个目标的重要信息工作programme的是，以确定如何在进化过程中修改的顺序分割机制，涉及到一个分割时钟产生的机制控制同时形成的果蝇节。确定基因调控的变化，促进这一转变可能会揭示一般原则，发展机制的演变，以产生各种各样的动物身体的计划，我们看到在natury.The第三个目标，这项工作计划是开发新的遗传技术，将推进赤拟谷盗作为一种廉价的，顺从的，道德上可接受的，无脊椎动物模型，研究分割时钟。公众将从这项研究中受益，通过增加我们对人类和动物进化的理解，通过开发一个强大的无脊椎动物遗传模型来研究分割时钟背后的遗传原理，从而减少目前对伦理上可接受的脊椎动物模型的依赖，并通过使用Tribolium，从未来对分割时钟的研究中获得更好的性价比，一种更便宜且可能更适合脊椎动物模型的替代品。

This research will identify important similarities and differences in the way animals as diverse as arthropods (i.e. fruit flies, beetles and spiders) and vertebrates (i.e. fish, mice and humans) develop their body during embryogenesis. This work is crucial for understanding how the genetic and developmental mechanisms forming animal body plans changed and diverged over evolutionary time to produce the diverse types of animal body plans we see in nature today. It is also important for understanding how the common ancestor of all animals developed its body plan, deep in evolutionary history, over 550 million years ago. Humans, and other vertebrates, possess a segmented body plan: internal parts of our body are divided into separated and repeated structures, for example our vertebrae and ribs. Vertebrate embryos grow during their development, with head structures formed first and the trunk grown in an anterior to posterior sequence. During this process, the cell populations that will later give rise to ribs/vertebrae are determined early, and one-by-one, in an anterior to posterior sequence. This process is controlled by a network of genes that are repeatedly turned on and off to define each group of cells (i.e. each future rib/vertebra). This complex oscillating network of genes is called the vertebrate segmentation clock. Arthropods, including fruit flies, beetles and spiders, also have a visibly segmented body plan. The abdominal body segments of the red flour beetle Tribolium castaneum form sequentially, one-by-one, in an anterior to posterior progression during beetle development, in a process similar to that described above for vertebrates. I have recently shown that this developmental process is also controlled by a network of genes that oscillate to sequentially pattern abdominal segments - the arthropod segmentation clock. Interestingly, the fruit fly Drosophila melanogaster has evolved to speed up its development, such that all body segments form simultaneously in the egg in a process that is already well understood at the genetic level by biologists.The first objective of this work programme is to determine whether the gene network underlying the arthropod segmentation clock is organized in a similar way to the vertebrate segmentation clock. If striking similarities are found, it could suggest that the segmentation clock was a feature of the common ancestor of arthropods and vertebrates. Alternatively, if there are striking differences, it could suggest that disparate animal groups have evolved similar genetic mechanisms independently and in parallel. Either way, this research promises to reveal important information about our evolutionary history.The second objective of this work programme is to determine how a sequential segmentation mechanism involving a segmentation clock was modified in evolution to produce the mechanism controlling the simultaneous formation of segments in Drosophila. Identifying the changes in gene regulation that facilitated this transition could reveal general principles by which developmental mechanisms evolved to produce the wide variety of animal body plans we see in nature today.The third objective of this work programme is to develop new genetic techniques that will advance Tribolium castaneum as a cheap, amenable, ethically acceptable, invertebrate model with which to study segmentation clocks. The general public will benefit from this research via an increase in our understanding of human and animal evolution, through the development of a powerful invertebrate genetic model for studying the genetic principles underlying segmentation clocks thus reducing the current dependence on less ethically acceptable vertebrate models, and through better value for money from future research on segmentation clocks via the use of Tribolium, a cheaper and potentially more amenable alternative to vertebrate models.