Insect larvae metamorphose to winged and reproductive adults either directly (hemimetaboly) or through an intermediary pupal stage (holometaboly). In either case juvenile hormone (JH) prevents metamorphosis until a larva has attained an appropriate phase of development. In holometabolous insects, JH acts through its putative receptor Methoprene-tolerant (Met) to regulate Krüppel-homolog 1 (Kr-h1) and Broad-Complex (BR-C) genes. While Met and Kr-h1 prevent precocious metamorphosis in pre-final larval instars, BR-C specifies the pupal stage. How JH signaling operates in hemimetabolous insects is poorly understood. Here, we compare the function of Met, Kr-h1 and BR-C genes in the two types of insects. Using systemic RNAi in the hemimetabolous true bug, Pyrrhocoris apterus, we show that Met conveys the JH signal to prevent premature metamorphosis by maintaining high expression of Kr-h1. Knockdown of either Met or Kr-h1 (but not of BR-C) in penultimate-instar Pyrrhocoris larvae causes precocious development of adult color pattern, wings and genitalia. A natural fall of Kr-h1 expression in the last larval instar normally permits adult development, and treatment with an exogenous JH mimic methoprene at this time requires both Met and Kr-h1 to block the adult program and induce an extra larval instar. Met and Kr-h1 therefore serve as JH-dependent repressors of deleterious precocious metamorphic changes in both hemimetabolous and holometabolous juveniles, whereas BR-C has been recruited for a new role in specifying the holometabolous pupa. These results show that despite considerable evolutionary distance, insects with diverse developmental strategies employ a common-core JH signaling pathway to commit to adult morphogenesis.

Biology Center Academy of Sciences of the Czech Republic Ceske Budejovice Czech Republic

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Sehnal F, Svacha P, Zrzavy J. Evolution of insect metamorphosis. In: Gilbert LI, Tata JR, Atkinson BG, editors. Metamorphosis. Postembryonic reprogramming of gene expression in amphibian and insect cells. San Diego: Academic Press; 1996. pp. 3–58.

Kristensen N. Phylogeny of endopterygote insects, the most successful lineage of living organisms. Eur J Entomol. 1999;96:237–253.

Gilbert LI, Granger NA, Roe RM. The juvenile hormones: historical facts and speculations on future research directions. Insect Biochem Mol Biol. 2000;30:617–644. PubMed

Nijhout H. Insect hormones. Princeton: Princeton University Press; 1994. 267

Riddiford L. Cellular and molecular actions of juvenile hormone. I. General considerations and premetamorphic actions. Adv Insect Physiol. 1994;24:213–274.

Fukuda S. The hormonal mechanism of larval molting and metamorphosis in the silkworm. J Fac Sci Tokyo Univ sec IV. 1944;6:477–532.

Wigglesworth V. The physiology of insect metamorphosis. Cambridge: Cambridge University Press; 1954. 152

Williams C. The juvenile hormone. II. Its role in the endocrine control of molting, pupation, and adult development in the Cecropia silkworm. Biol Bull. 1961;116:323–338.

Wigglesworth V. The physiology of ecdysis in Rhodnius prolixus (Hemiptera). II. Factors controlling moulting and “metamorphosis.”. Quart J Micr Sci. 1934;77:191–222.

Wigglesworth V. The function of the corpus allatum in the growth and reproduction of Rhodnius prolixus (Hemiptera). Quart J Micr Sci. 1936;79:91–121.

Wilson TG, Fabian J. A Drosophila melanogaster mutant resistant to a chemical analog of juvenile hormone. Dev Biol. 1986;118:190–201. PubMed

Ashok M, Turner C, Wilson TG. Insect juvenile hormone resistance gene homology with the bHLH-PAS family of transcriptional regulators. Proc Natl Acad Sci U S A. 1998;95:2761–2766. PubMed PMC

Konopova B, Jindra M. Juvenile hormone resistance gene Methoprene-tolerant controls entry into metamorphosis in the beetle Tribolium castaneum. Proc Natl Acad Sci U S A. 2007;104:10488–10493. doi: 10.1073/pnas.0703719104. PubMed DOI PMC

Minakuchi C, Namiki T, Yoshiyama M, Shinoda T. RNAi-mediated knockdown of juvenile hormone acid O-methyltransferase gene causes precocious metamorphosis in the red flour beetle Tribolium castaneum. FEBS J. 2008;275:2919–2931. doi: 10.1111/j.1742-4658.2008.06428.x. PubMed DOI

Parthasarathy R, Tan A, Palli SR. bHLH-PAS family transcription factor methoprene-tolerant plays a key role in JH action in preventing the premature development of adult structures during larval–pupal metamorphosis. Mech Dev. 2008;125:601–616. doi: 10.1016/j.mod.2008.03.004. PubMed DOI PMC

Konopova B, Jindra M. Broad-Complex acts downstream of Met in juvenile hormone signaling to coordinate primitive holometabolan metamorphosis. Development. 2008;135:559–568. doi: 10.1242/dev.016097. PubMed DOI

Minakuchi C, Namiki T, Shinoda T. Krüppel homolog 1, an early juvenile hormone-response gene downstream of Methoprene-tolerant, mediates its anti-metamorphic action in the red flour beetle Tribolium castaneum. Dev Biol. 2009;325:341–350. doi: 10.1016/j.ydbio.2008.10.016. PubMed DOI

Minakuchi C, Zhou X, Riddiford LM. Krüppel homolog 1 (Kr-h1) mediates juvenile hormone action during metamorphosis of Drosophila melanogaster. Mech Dev. 2008;125:91–105. doi: 10.1016/j.mod.2007.10.002. PubMed DOI PMC

Kiss I, Beaton AH, Tardiff J, Fristrom D, Fristrom JW. Interactions and developmental effects of mutations in the Broad-Complex of Drosophila melanogaster. Genetics. 1988;118:247–259. PubMed PMC

Zhou X, Riddiford LM. Broad specifies pupal development and mediates the “status quo” action of juvenile hormone on the pupal-adult transformation in Drosophila and Manduca. Development. 2002;129:2259–2269. PubMed

Uhlirova M, Foy BD, Beaty BJ, Olson KE, Riddiford LM, et al. Use of Sindbis virus-mediated RNA interference to demonstrate a conserved role of Broad-Complex in insect metamorphosis. Proc Natl Acad Sci U S A. 2003;100:15607–15612. doi: 10.1073/pnas.2136837100. PubMed DOI PMC

Suzuki Y, Truman JW, Riddiford LM. The role of Broad in the development of Tribolium castaneum: implications for the evolution of the holometabolous insect pupa. Development. 2008;135:569–577. doi: 10.1242/dev.015263. PubMed DOI

Parthasarathy R, Tan A, Bai H, Palli SR. Transcription factor broad suppresses precocious development of adult structures during larval–pupal metamorphosis in the red flour beetle, Tribolium castaneum. Mech Dev. 2008;125:299–313. doi: 10.1016/j.mod.2007.11.001. PubMed DOI PMC

Erezyilmaz DF, Rynerson MR, Truman JW, Riddiford LM. The role of the pupal determinant broad during embryonic development of a direct-developing insect. Dev. Genes Evol. 2010;219:535–544. doi: 10.1007/s00427-009-0315-7. PubMed DOI PMC

Piulachs M-D, Pagone V, Bellés X. Key roles of the Broad-Complex gene in insect embryogenesis. Insect Biochem Mol Biol. 2010;40:468–475. doi: 10.1016/j.ibmb.2010.04.006. PubMed DOI

Erezyilmaz DF, Riddiford LM, Truman JW. The pupal specifier broad directs progressive morphogenesis in a direct-developing insect. Proc Natl Acad Sci U S A. 2006;103:6925–6930. doi: 10.1073/pnas.0509983103. PubMed DOI PMC

Sláma K. Effect of hormones on growth and respiratory metabolism in the larvae of Pyrrhocoris apterus L. (Hemiptera). J Insect Physiol. 1965;11:113–122. PubMed

Sláma K, Williams CM. Juvenile hormone activity for the bug Pyrrhocoris apterus. Proc Natl Acad Sci U S A. 1965;54:411–414. PubMed PMC

Willis J, Rezaur R, Sehnal F. Juvenoids cause some insects to form composite cuticles. J Embryol Exp Morph. 1982;71:25–40. PubMed

Nijhout H. Definition of a juvenile hormone-sensitive period in Rhodnius prolixus. J Insect Physiol. 1983;29:669–677.

Novak V. Insect hormones. London: Methuen & Co. Ltd; 1966. 478

Truman JW, Riddiford LM. The origins of insect metamorphosis. Nature. 1999;401:447–452. doi: 10.1038/46737. PubMed DOI

Truman JW, Riddiford LM. Endocrine insights into the evolution of metamorphosis in insects. Annu Rev Entomol. 2002;47:467–500. doi: 10.1146/annurev.ento.47.091201.145230. PubMed DOI

Belles X. Origin and evolution of insect metamorphosis. Chichester: John Wiley & Sons, Ltd; 2011. doi: 10.1002/9780470015902.a0022854. DOI

Hinton H. The origin and function of the pupal stage. Proc R Ent Soc Lond. 1963;38:77–85.

Dolezel D, Zdechovanova L, Sauman I, Hodkova M. Endocrine-dependent expression of circadian clock genes in insects. Cell Mol Life Sci. 2008;65:964–969. doi: 10.1007/s00018-008-7506-7. PubMed DOI PMC

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