Silva Valeria, Scott Robert, Guajardo Paulina, Luan Haojiang, Herzog Ruben, White Benjamin H, Ewer John
bioRxiv. 2025 May 4:2025.04.03.646974. doi: 10.1101/2025.04.03.646974.
Neuromodulators and peptide hormones play important roles in regulating animal behavior. A well-studied example is ecdysis, which is used by insects to shed their exoskeleton at the end of each molt. Ecdysis is initiated by Ecdysis Triggering Hormone (ETH) and Eclosion Hormone (EH), which interact via positive feedback to coordinate the sequence of behavioral and physiological changes that cause exoskeleton shedding. Whereas the cell types targeted by ETH are well characterized, those targeted by EH have remained largely unknown due to limited characterization of the EH receptor (EHR). A gene encoding an EHR has been described in the oriental fruit fly, , and in the desert locust, . However, little is known in these species about its expression pattern and its precise role at ecdysis, and no other insect EHRs are known. Here we analyze CG10738, the ortholog of the gene encoding EHR, and show that expressing it in cells confers sensitivity to EH. In addition, mutations of CG10738 specifically disrupt ecdysis, phenocopying the knockout of the EH gene. Together, these results indicate that CG10738 encodes the EHR. As in , EHR is expressed in the ETH-producing Inka cells; in addition, it is expressed in many known targets of ETH, including the neurons responsible for the secretion of other ecdysis-related peptides, such as CCAP and EH itself. Our results from targeted knockdown and rescue experiments reveal that EHR is required for ecdysis in diverse cell types and that the role of EHR in different targets differs with developmental stage. Our findings indicate extensive convergence of EH and ETH signaling and provide an exemplar of the complex mechanisms by which hormones control animal behavior.
Hormones and neuromodulators are important regulators of animal behavior. In insects, one of the best studied behaviors influenced by hormones is ecdysis, which allows the animal to shed the remains of its exoskeleton at the end of each molt. Ecdysis is controlled by two key hormones: Ecdysis Triggering Hormone (ETH) and Eclosion Hormone (EH). Whereas most targets of ETH have been identified, those of EH have remained largely unknown due to the limited characterization of its receptor, EHR. Previous studies identified a gene encoding EHR in the oriental fruit fly, , and in the desert locust, but little is known about its expression pattern or its precise role. Here, we show that CG10738 encodes the EHR. We found that EHR is expressed in ETH-producing Inka cells, in neurons that secrete other ecdysis-related peptides, in addition to other neuronal classes and non-neuronal cells. Targeted knockdown and rescue experiments revealed that EHR is essential for ecdysis in various cell types, and that its role can vary depending on the developmental stage. Our findings reveal that the role of EH at ecdysis is complex and provides insights into how hormones and neuromodulators regulate animal behavior.
神经调质和肽类激素在调节动物行为中发挥着重要作用。一个被充分研究的例子是蜕皮，昆虫在每次蜕皮结束时会利用这一过程蜕去外骨骼。蜕皮由蜕皮触发激素（ETH）和羽化激素（EH）启动，它们通过正反馈相互作用，以协调导致外骨骼脱落的行为和生理变化序列。虽然ETH作用的细胞类型已得到充分表征，但由于EH受体（EHR）的表征有限，EH作用的细胞类型在很大程度上仍不清楚。在东方果实蝇和沙漠蝗虫中已描述了一个编码EHR的基因。然而，对于这些物种中该基因的表达模式及其在蜕皮时的确切作用知之甚少，并且尚未发现其他昆虫的EHR。在这里，我们分析了编码EHR的基因的直系同源基因CG10738，并表明在细胞中表达它会赋予细胞对EH的敏感性。此外，CG10738的突变会特异性地破坏蜕皮，模拟EH基因敲除的表型。这些结果共同表明CG10738编码EHR。与在[具体物种1]中一样，EHR在产生ETH的印卡细胞中表达；此外，它还在许多已知的ETH作用靶点中表达，包括负责分泌其他与蜕皮相关肽的神经元，如CCAP和EH本身。我们从靶向敲低和拯救实验中得到的结果表明，EHR在多种细胞类型的蜕皮过程中是必需的，并且EHR在不同靶点中的作用因发育阶段而异。我们的发现表明EH和ETH信号存在广泛的趋同，并提供了一个激素控制动物行为的复杂机制的范例。
激素和神经调质是动物行为的重要调节因子。在昆虫中，受激素影响研究得最充分的行为之一是蜕皮，这使动物能够在每次蜕皮结束时蜕去外骨骼的残余部分。蜕皮由两种关键激素控制：蜕皮触发激素（ETH）和羽化激素（EH）。虽然ETH的大多数靶点已被确定，但由于其受体EHR的表征有限，EH的靶点在很大程度上仍不清楚。先前的研究在东方果实蝇和沙漠蝗虫中鉴定出一个编码EHR的基因，但对其表达模式或确切作用知之甚少。在这里，我们表明CG10738编码EHR。我们发现EHR在产生ETH的印卡细胞、分泌其他与蜕皮相关肽的神经元以及其他神经元类别和非神经元细胞中表达。靶向敲低和拯救实验表明，EHR在各种细胞类型的蜕皮过程中至关重要，并且其作用可能因发育阶段而异。我们的发现揭示了EH在蜕皮时的作用是复杂的，并为激素和神经调质如何调节动物行为提供了见解。
