Endocrine scaffolds and peptide networks: How is the molt cycle and ecdysis programme controlled in crustaceans?

内分泌支架和肽网络：甲壳类动物的蜕皮周期和蜕皮程序是如何控制的？

• 批准号: BB/T005912/1
• 负责人: Simon Webster
• 金额: $ 75.3万
• 依托单位: Bangor University
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FT005912%2F1
• 关键词: Endocrine; scaffolds; peptide; networks; How

Arthropods are the most successful multicellular organisms on earth, in terms of diversity, species number and habitat utilisation. Arguably, they are the most important on earth; providing key ecosystem roles, as pollinators, pests and vectors of disease, yet many, for example crustaceans, are high value food resources. Their success is due to their growth format, which involves periodic shedding of the exoskeleton to allow growth, and development. Recently, there has been an explosion of information regarding the nature of insect peptide hormones, and the genetic tractability of several model insect species, together with genome and transcriptome analyses has led to dramatic, indeed fundamental advances in our knowledge of the hormonal control of insect ecdysis programmes. However, in comparison, knowledge of the equivalent processes in crustaceans is far less well developed. Whilst arthropods share a common ancestry, (having diverged over 500mya), which is beautifully reflected in the similarity of many of the peptides and receptors of insects and crustaceans, there has been a divergence in function of a number of these. This is illustrated nicely when comparing molt control in crustaceans and insects: The core components involved in stereotyped behaviours involved in emergence from the old exoskeleton (the "ecdysis cassette") are similar, yet the control mechanisms that drive increases in molting hormone synthesis are entirely different. We have recently discovered a novel neuropeptide signalling system (corazonin- CRZ) which targets the molting gland (Y-organ) that will completely reappraise models of crustacean molting with regard to the control of ecdysteroid synthesis. In between these (premolt initiation and ecdysis), we have discovered tantalising glimpses of a peptide and receptor signalling system (ecdysis triggering hormone, ETH, and eclosion hormone, EH) which appears to be homologous to those in insects, but for which we have no functional information in crustaceans.In this project, the over-arching objective is to unravel the complexities of neuropeptide/receptor signalling involved in the three phases of the molt cycle outlined here, using our well established crab (Carcinus maenas) model. Firstly, will investigate the novel role of CRZ signalling in relation to its proposed role in controlling the action of the molt-inhibiting hormone (MIH) and crustacean hyperglycemic hormone CHH that will likely be a key control in entry into premolt. Since the receptors for these hormones have not been identified, we will identify and functionally characterise these by a single transcript sequencing and bioinformatics approach, whereby full length transcript sequences of putative receptors expressed by the Y-organ will be identified, followed by functional "deorphaning" in heterologous expression systems. Secondly, we will identify the peptide signalling pathway and expression of ETH and EH and their cognate receptors, which are thus far only known in insects using the approaches alluded to here. Finally we aim to discover the roles of these hormone signalling systems in the ultimate stage of molting- the precisely integrated behavioural and hormonal cascades involved in ecdysis using a targeted approach. We will manipulate or disrupt the ecdysis "cassette" by altering expression and/or timing of release of these hormones, which will involve determining alterations in the sequential release of key hormones during ecdysis.The proposed research will firstly answer the big question in crustacean endocrinology: How is ecdysis controlled? Furthermore, it has direct potential application and benefits to aquaculture, since it is translational. We propose that the hormonal control mechanisms that we identify in a crab model will, since these are core processes, be directly translatable to shrimp aquaculture, where there is almost no knowledge of functional characterised neuroendocrine control of ecdysis.

就多样性、物种数量和栖息地利用而言，节肢动物是地球上最成功的多细胞生物。可以说，它们是地球上最重要的；提供关键的生态系统角色，如传粉者、害虫和疾病媒介，但许多是高价值的食物资源，例如甲壳类动物。它们的成功归功于它们的生长模式，这涉及到周期性的外骨骼脱落，以允许生长和发育。最近，关于昆虫多肽激素性质的信息爆炸式增长，几个模式昆虫物种的遗传易操纵性，加上基因组和转录组分析，使我们对昆虫蜕皮程序的激素控制的知识取得了戏剧性的、甚至是根本性的进展。然而，与之相比，甲壳类中的等同过程的知识远远不那么发达。虽然节肢动物有着共同的祖先(分歧超过500英里)，这很好地反映在昆虫和甲壳类动物的许多肽和受体的相似性上，但其中一些在功能上存在分歧。在比较甲壳类动物和昆虫的蜕皮控制时，这一点得到了很好的说明：旧的外骨骼(蜕皮盒)中涉及的刻板行为所涉及的核心成分相似，但推动蜕皮激素合成增加的控制机制完全不同。我们最近发现了一种针对蜕皮腺(Y器官)的新的神经肽信号系统(Corazin-CRZ)，它将在控制蜕皮类固醇合成方面完全重新评估甲壳动物蜕皮的模型。在这些(蜕皮前启动和蜕皮)之间，我们发现了诱人的一瞥多肽和受体信号系统(蜕皮触发激素，ETH和羽化激素，EH)，它似乎与昆虫中的同源，但我们在甲壳类中没有功能信息。在这个项目中，总体目标是利用我们已经建立的螃蟹(Carcinus Maenas)模型，揭开在这里概述的蜕皮周期的三个阶段中神经肽/受体信号传递的复杂性。首先，将研究CRZ信号在控制蜕皮抑制激素(MIH)和甲壳类高血糖激素CHH的作用方面的新作用，这可能是进入预蜕皮的关键控制。由于这些激素的受体尚未确定，我们将通过单一的转录测序和生物信息学方法来鉴定和鉴定这些激素的受体，从而确定Y器官表达的假定受体的全长转录序列，然后在异源表达系统中进行功能性的“去孤儿”。其次，我们将利用这里提到的方法来鉴定ETH和EH及其同源受体的肽信号通路和表达，到目前为止，这些受体只在昆虫中已知。最后，我们的目标是发现这些激素信号系统在蜕皮的最终阶段的作用-使用有针对性的方法，精确地整合涉及蜕皮的行为和荷尔蒙级联。我们将通过改变这些激素的表达和/或释放的时间来操纵或破坏蜕皮盒，这将涉及确定蜕皮期间关键激素顺序释放的变化。拟议的研究将首先回答甲壳类内分泌学的一个大问题：蜕皮是如何控制的？此外，由于它是可转化的，因此在水产养殖中具有直接的潜在应用和好处。我们建议，我们在螃蟹模型中识别的激素控制机制将直接翻译到对虾水产养殖中，因为这些是核心过程，对虾水产养殖几乎没有关于蜕皮的功能性特征神经内分泌控制的知识。