Investigating the molecular mechanisms underpinning the arthropod segmentation clock

节肢动物表现出全身的节段性，而在脊椎动物中，只有内部的中胚层衍生品是节段性的，包括脊椎骨和肌肉。皮尔博士的工作表明，支持节肢动物和脊椎动物节段结构形成的发育遗传网络在机制上有惊人的相似之处；在这两个门的节段中，都是在分子振荡器网络的控制下形成的，这些分子振荡器网络一起被称为“节段钟”。这个项目将研究红色面粉甲虫Tribolium Castaneum的片段网络，与果蝇不同，它使用片段时钟顺序生成片段。该项目将确定Notch信号通路及其下游靶标-毛发/分裂增强因子(HES)家族转录因子(TF)-是否像在脊椎动物中一样，在Tribolium分段时钟中发挥核心作用。因此，这项研究将确定支撑节肢动物和脊椎动物分段时钟的机械相互作用的相似程度，并有助于确定Tribolium作为理解脊椎动物分段时钟的无脊椎动物模型的强大程度。这个项目将是第一个在蛋白质水平上考虑节肢动物节律时钟内发生的机械性相互作用的项目。该项目也将是第一个专门考虑中胚层(相对于外胚层)的分割机制，这是与脊椎动物更合适的比较点。

Arthropods exhibit whole body segmentation, while in vertebrates only internal mesodermal derivatives are segmented, including vertebrae and muscles. Dr Peel's work has shown that the developmental genetic networks underpinning the formation of segmented structures in arthropods and vertebrates share striking mechanistic similarities; in both phyla segments form under the control of a network of molecular oscillators, together termed the 'segmentation clock'. This project will investigate the segmentation network in the red flour beetle Tribolium castaneum, which, unlike Drosophila, generates its segments sequentially using a segmentation clock. The project will determine whether the Notch-signalling pathway and its downstream targets - the Hairy/Enhancer-of-split (HES)-family transcription factors (TFs) - play a central role within the Tribolium segmentation clock, as they do in vertebrates. This study will therefore determine the extent of similarity in the mechanistic interactions underpinning the arthropod and vertebrate segmentation clocks, and help determine how powerful Tribolium is as an invertebrate model for understanding the vertebrate segmentation clock. This project will be the first to consider mechanistic interactions occurring within the arthropod segmentation clock at the protein level. The project would also be the first to specifically consider the segmentation mechanisms operating within the mesoderm (as opposed to ectoderm), a more appropriate point of comparison to vertebrates.