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Decrease, Cuticular chitin content leads to Increase, Premature molting
Key Event Relationship Overview
AOPs Referencing Relationship
|AOP Name||Adjacency||Weight of Evidence||Quantitative Understanding||Point of Contact||Author Status||OECD Status|
|S-adenosylmethionine depletion leading to population decline (2)||adjacent||You Song (send email)||Under development: Not open for comment. Do not cite|
|S-adenosylmethionine depletion leading to population decline (1)||adjacent||You Song (send email)||Under development: Not open for comment. Do not cite|
|Chitin synthase 1 inhibition leading to mortality||adjacent||Moderate||Low||Simon Schmid (send email)||Open for citation & comment||WPHA/WNT Endorsed|
|Sulfonylureareceptor binding leading to mortality||adjacent||Moderate||Moderate||Simon Schmid (send email)||Under development: Not open for comment. Do not cite||Under Development|
Life Stage Applicability
Key Event Relationship Description
As the arthropod cuticle is a central part in the molting process, its proper composition is indispensable for a proper molt. The ecdysis motor program, the behavioral part of ecdysis, constitutes a distinct motor pattern to split and shed the old cuticle (Ayali 2009). As the cuticle supports muscular function (Vincent and Wegst 2004), it needs to possess a certain integrity in order to successfully molt. The integrity of the cuticle is also important after ecdysis as arthropods, such as insects and crustaceans, expand the new cuticle by swallowing air or water in order to build up pressure to split the old and expand the new exoskeleton and provide stability to the soft new cuticle (Clarke 1957; Lee 1961; Dall et al. 1978; deFur et al. 1985). The arthropod cuticle mostly consists of chitin embedded in and crosslinked with a matrix of proteins (Muthukrishnan et al. 2012). If the chitin content is too low, the cuticle may not possess enough integrity to support muscular function or withstand the beforementioned stresses of ecdysis, which leads to the organism being stuck in the old cuticle or the rupture of the new cuticle.
Evidence Collection Strategy
Evidence Supporting this KER
The ecdysis motor program, the behavioral part of ecdysis, constitutes a distinct motor pattern to split and shed the old cuticle (Ayali 2009). As the cuticle supports muscular function (Vincent and Wegst 2004), it needs to possess a certain integrity in order to successfully molt. The integrity of the cuticle is also important after ecdysis as arthropods, such as insects and crustaceans, expand the new cuticle by swallowing air or water in order to build up pressure to expand the new exoskeleton and provide stability to the soft new cuticle (Clarke 1957; Lee 1961; Dall et al. 1978; deFur et al. 1985). The arthropod cuticle mostly consists of chitin embedded in and crosslinked with a matrix of proteins (Muthukrishnan et al. 2012). Given the well biological understanding of the processes, the biological plausibility can be regarded as high.
The cuticular chitin content was characterized in vivo in Artemia salina or using cultured integumental tissue from lepidopteran and dipteran insect species after exposure to polyoxin D and nikkomycin Z as well as the phthalimides captan, captafol, and folpet (Gijswijt et al. 1979; Turnbull and Howells 1982; Calcott and Fatig 1984; Gelman and Borkovec 1986; Zhuo et al. 2014). The event of premature molting was not assessed as endpoint in studies involving specific stressors rather than mentioned after exposure to polyoxin D, polyoxin B and nikkomycin Z (Gijswijt et al. 1979; Tellam et al. 2000; Arakawa et al. 2008). However, results from studies where CHS-1 was knocked down by RNA interference support temporal concordance of the KER (Arakane et al. 2005, Li et al. 2017, Zhang X. et al. 2010). Given the support for temporal concordance and the lack of studies showing dose concordance, the empirical evidence for this KER was judged as moderate.
Uncertainties and Inconsistencies
The absence of studies (quantitatively) assessing premature molting constitutes a major data gap. A further data gap is the absence of studies which assess both, the decrease in cuticular chitin content and the increase in premature molting.
Known modulating factors
Quantitative Understanding of the Linkage
Due to the lack of studies linking the decrease in cuticular chitin content with the increase in premature molting, it is not possible to describe the nature of the response-response relationship.
Due to the nature of the process, premature molting onsets at the time of ecdysis after the decrease in cuticular chitin content.
Known Feedforward/Feedback loops influencing this KER
Domain of Applicability
Taxonomic: In all likelihood, this KER is applicable to the whole phylum of arthropods as they all depend on the synthesis of chitin and molting in order to develop.
Life stage: This KER is applicable for organisms synthesizing chitin and molting in order to grow and develop, namely larval stages of insects and all life stages of crustaceans and arachnids.
Sex: This KER is applicable to all sexes.
Chemical: Occurrence of a decrease in cticular chitin content as well as premature molting was observed after treatment with the pyrimidine nucleosides polyoxin D, polyoxin B and nikkomycin Z (Gijswijt et al. 1979; Turnbull and Howells 1982; Calcott and Fatig 1984; Gelman and Borkovec 1986; Tellam et al. 2000; Arakawa et al. 2008; Zhuo et al. 2014). However, studies causally linking both endpoints are lacking.
Arakane, Y.; Muthukrishnan, S.; Kramer, K. J.; Specht, C. A.; Tomoyasu, Y.; Lorenzen, M. D.; Kanost, M.; Beeman, R. W. The Tribolium Chitin Synthase Genes TcCHS1 and TcCHS2 Are Specialized for Synthesis of Epidermal Cuticle and Midgut Peritrophic Matrix. Insect Mol. Biol. 2005, 14 (5), 453–463. https://doi.org/10.1111/j.1365-2583.2005.00576.x.
Arakawa T, Yukuhiro F, Noda H. 2008. Insecticidal effect of a fungicide containing polyoxin B on the larvae of Bombyx mori (Lepidoptera: Bombycidae), Mamestra brassicae, Mythimna separata, and Spodoptera litura (Lepidoptera: Noctuidae). Appl Entomol Zool. 43(2):173–181. doi:10.1303/aez.2008.173.
Ayali A. 2009. The role of the arthropod stomatogastric nervous system in moulting behaviour and ecdysis. J Exp Biol. 212(4):453–459. doi:10.1242/jeb.023879.
Calcott PH, Fatig RO. 1984. Inhibition of Chitin metabolism by Avermectin in susceptible Organisms. J Antibiot (Tokyo). 37(3):253–259. doi:10.7164/antibiotics.37.253.
Clarke KU. 1957. On the Increase in Linear Size During Growth in Locusta Migratoria L. Proc R Entomol Soc London Ser A, Gen Entomol. 32(1–3):35–39. doi:10.1111/j.1365-3032.1957.tb00361.x.
Dall W, Smith DM, Press B. 1978. Water uptake at ecdysis in the western rock lobster. J Exp Mar Bio Ecol. 35(1960). doi:10.1016/0022-0981(78)90074-6.
deFur PL, Mangum CP, McMahon BR. 1985. Cardiovascular and Ventilatory Changes During Ecdysis in the Blue Crab Callinectes Sapidus Rathbun. J Crustac Biol. 5(2):207–215. doi:10.2307/1547867.
Gelman DB, Borkovec AB. 1986. The pharate adult clasper as a tool for measuring chitin synthesis and for identifying new chitin synthesis inhibitors. Comp Biochem Physiol Part C, Comp. 85(1):193–197. doi:10.1016/0742-8413(86)90073-3.
Gijswijt MJ, Deul DH, de Jong BJ. 1979. Inhibition of chitin synthesis by benzoyl-phenylurea insecticides, III. Similarity in action in Pieris brassicae (L.) with Polyoxin D. Pestic Biochem Physiol. 12(1):87–94. doi:10.1016/0048-3575(79)90098-1.
Lee RM. 1961. The variation of blood volume with age in the desert locust (Schistocerca gregaria Forsk.). J Insect Physiol. 6(1):36–51. doi:10.1016/0022-1910(61)90090-7.
Li, T.; Chen, J.; Fan, X.; Chen, W.; Zhang, W. MicroRNA and DsRNA Targeting Chitin Synthase A Reveal a Great Potential for Pest Management of the Hemipteran Insect Nilaparvata Lugens. Pest Manag. Sci. 2017, 73 (7), 1529–1537. https://doi.org/10.1002/ps.4492.
Muthukrishnan S, Merzendorfer H, Arakane Y, Kramer KJ. 2012. Chitin Metabolism in Insects. Elsevier B.V. http://dx.doi.org/10.1016/B978-0-12-384747-8.10007-8.
Tellam RL, Vuocolo T, Johnson SE, Jarmey J, Pearson RD. 2000. Insect chitin synthase. cDNA sequence, gene organization and expression. Eur J Biochem. 267(19):6025–6043. doi:10.1046/j.1432-1327.2000.01679.x.
Turnbull IF, Howells AJ. 1982. Effects of several larvicidal compounds on chitin biosynthesis by isolated larval integuments of the sheep blowfly Lucilia cuprina. Aust J Biol Sci. 35(5):491–504. doi:10.1071/BI9820491.
Vincent JFV, Wegst UGK. 2004. Design and mechanical properties of insect cuticle. Arthropod Struct Dev. 33(3):187–199. doi:10.1016/j.asd.2004.05.006.
Zhang, X.; Zhang, J.; Zhu, K. Y. Chitosan/Double-Stranded RNA Nanoparticle-Mediated RNA Interference to Silence Chitin Synthase Genes through Larval Feeding in the African Malaria Mosquito (Anopheles Gambiae). Insect Mol. Biol. 2010, 19 (5), 683–693. https://doi.org/10.1111/j.1365-2583.2010.01029.x.
Zhuo W, Fang Y, Kong L, Li X, Sima Y, Xu S. 2014. Chitin synthase A: A novel epidermal development regulation gene in the larvae of Bombyx mori. Mol Biol Rep. 41(7):4177–4186. doi:10.1007/s11033-014-3288-1.