Please do not remove this page The crustacean ecdysone cassette: a gatekeeper for molt and metamorphosis Hyde, Cameron J; Elizur, Abigail; Ventura, Tomer https://research.usc.edu.au/discovery/delivery/61USC_INST:ResearchRepository/12126573000002621?l#13127277830002621 Hyde, C. J., Elizur, A., & Ventura, T. (2019). The crustacean ecdysone cassette: a gatekeeper for molt and metamorphosis. Journal of Steroid Biochemistry and Molecular Biology, 185, 172–183. https://doi.org/10.1016/j.jsbmb.2018.08.012 Document Type: Accepted Version Link to Published Version: https://doi.org/10.1016/j.jsbmb.2018.08.012 USC Research Bank: https://research.usc.edu.au [email protected] CC BY-NC-ND V4.0 Copyright © 2019. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ The final version is available at DOI:10.1016/j.jsbmb.2018.08.012 Downloaded On 2021/10/02 22:23:43 +1000 Please do not remove this page Accepted Manuscript Title: The crustacean ecdysone cassette: A gatekeeper for molt and metamorphosis Authors: Cameron J. Hyde, Abigail Elizur, Tomer Ventura PII: S0960-0760(18)30265-6 DOI: https://doi.org/10.1016/j.jsbmb.2018.08.012 Reference: SBMB 5202 To appear in: Journal of Steroid Biochemistry & Molecular Biology Received date: 10-5-2018 Revised date: 21-8-2018 Accepted date: 25-8-2018 Please cite this article as: Hyde CJ, Elizur A, Ventura T, The crustacean ecdysone cassette: A gatekeeper for molt and metamorphosis, Journal of Steroid Biochemistry and Molecular Biology (2018), https://doi.org/10.1016/j.jsbmb.2018.08.012 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. The crustacean ecdysone cassette: a gatekeeper for molt and metamorphosis Running title: Endocrinology of crustacean metamorphosis Cameron J. Hyde, Abigail Elizur and Tomer Ventura Genecology Research Centre, Faculty of Science, Health, Education and Engineering, University of the Sunshine Coast, 4 Locked Bag, Maroochydore, Queensland 4558, Australia Graphical abstract Highlights: Metamorphosis regulation with emphasis on crustaceans is reviewed ACCEPTED Specific attention is given to the ecdysone MANUSCRIPT pathway and associated nuclear receptors Gaps in knowledge are identified and future directions are suggested 1 Abstract Arthropods have long been utilized as models to explore molecular function, and the findings derived from them can be applied throughout metazoa, including as a basis for medical research. This has led to the adoption of many representative insect models beyond Drosophila, as each lends its own unique perspective to questions in endocrinology and genetics. However, non- insect arthropods are yet to be realised for the potential insight they may provide in such studies. The Crustacea are among the most ancient arthropods from which insects descended, comprising a huge variety of life histories and ecological roles. Of the events in a typical crustacean development, metamorphosis is perhaps the most ubiquitous, challenging and highly studied. Despite this, our knowledge of the endocrinology which underpins metamorphosis is rudimentary at best; although several key molecules have been identified and studied in depth, the link between them is quite nebulous and leans heavily on well-explored insect models, which diverged from the Pancrustacea over 450 million years ago. As omics technologies become increasingly accessible, they bring the prospect of explorative molecular research which will allow us to uncover components and pathways unique to crustaceans. This review reconciles known components of crustacean metamorphosis and reflects on our findings in insects to outline a future search space, with focus given to the ecdysone cascade. To expand our knowledge of this ubiquitous endocrine system not only aids in our understanding of crustacean metamorphosis, but also provides a deeper insight into the adaptive capacity of arthropods throughout evolution. Keywords: Arthropod, Ecdysone, Endocrine, Methyl farnesoate, Molt, Nuclear receptor ACCEPTED MANUSCRIPT 2 Table of Contents Introduction ..................................................................................................................................................... 4 Endocrinology of molting ........................................................................................................................... 9 Endocrinology of metamorphosis ........................................................................................................ 12 Nuclear receptor function ....................................................................................................................... 16 Intercepting the ecdysone cassette ...................................................................................................... 19 Conclusion ..................................................................................................................................................... 23 Acknowledgements .................................................................................................................................... 25 References ..................................................................................................................................................... 25 ACCEPTED MANUSCRIPT 3 1. Introduction Over the past century, model organisms have emerged as a vital tool for exploring physiology, disease and genetics, providing a platform for insights into biological phenomena which can be applied across taxa. The most fruitful metazoan model organism to date is without a doubt Drosophila melanogaster, whose ease of laboratory rearing and abundance of phenotypes made them an ideal candidate for pioneering exploration of gene function in vivo. As knowledge was transferred to other insect species, complimentary insect models arose to represent the physiological and genetic distinctions between the insect orders, such as holometabolous (complete metamorphosis) and hemimetabolous (incomplete metamorphosis) development. This iterative expansion of knowledge and variety of biological perspectives has cultivated a very comprehensive understanding of endocrine pathways and corresponding genes in the insects. The wealth of information accumulated in the insects has provided non-insect researchers with a valuable reference to guide them through novel ventures which would otherwise have been impossible, and a convention arose whereby unexplored species are systematically unravelled through comparison with an appropriate model. This approach is particularly amenable to genetic and endocrine applications, since analogous components are often shared among classes and even across phyla, but its utility is generally limited to the transfer of only fundamental concepts, which must be drawn out and contextualized in the species of interest. For example, a conserved enzyme likely binds a similar substrate to its homolog, but gene expression, specificity and binding kinetics are likely to be different. Phylogenetic analysis has found the Hexapod clade to be an ancient divergent of the Pancrustacea and therefore, evolutionarily speaking, insects can be considered as derived crustaceansACCEPTED [1, 2]. It is surprising then to find thatMANUSCRIPT our knowledge of crustacean endocrine regulation is comparatively sparse, and though much has been inferred from insect models there are frequent anomalies which cannot be explained by these distant relatives. Of course, the advent of ecdysis (molting) long predates the divergence of the Pancrustacean ancestor, and 4 thus the mechanism for molting is common to insects and crustaceans [1, 3]. It is well documented that arthropod molting is regulated by cyclical pulses of the steroid hormone ecdysone [4]. Downstream of the ecdysone receptor, a vast suite of genes are upregulated; the resulting transcriptomic shift coordinates cuticle release, osmotic flux, tissue remodelling and the many other physiological processes which orchestrate the molt. This widespread flux of gene expression is orchestrated by the ecdysone cassette (or ecdysone cascade), and involves many members of the nuclear receptor superfamily, including the ecdysone receptor itself, and its accurate profiling in Drosophila has provided significantly to our understanding of nuclear receptor function [5-9]. Our knowledge of the ecdysone cassette and the NR superfamily in crustaceans is comparatively limited with very few studies making a comprehensive curation of the NR family [10], which in Daphnia (Daphniidae) has been shown to comprise at least 25 genes [11]. Holistic characterisation of ecdysone response components could provide interesting and useful perspectives on steroid hormone function and nuclear receptor interactions, particularly in the context of metamorphosis. In this critical transformation, the ecdysone cassette is modified to instigate organism-wide tissue restructuring as the molt unfolds, and the animal which emerges from its spent cuticle often looks remarkably different than before [12, 13]. Although this adaptation of the ecdysone cassette has