title: Ecdysteroid promotes cell cycle progression in the Bombyx wing disc through activation of c-Myc.
abstract: Developmental switching from growth to metamorphosis in imaginal primordia is an essential process of adult body planning in holometabolous insects. Although it is disciplined by a sequential action of the ecdysteroid, molecular mechanisms linking to cell proliferation are poorly understood. In the present study, we investigated the expression control of cell cycle-related genes by the ecdysteroid using the wing disc of the final-instar larvae of the silkworm, Bombyx mori. We found that the expression level of c-myc was remarkably elevated in the post-feeding cell proliferation phase, which coincided with a small increase in ecdysteroid titer. An in vitro wing disc culture showed that supplementation of the moderate level of the ecdysteroid upregulated c-myc expression within an hour and subsequently increased the expression of cell cycle core regulators, including A-, B-, D-, and E-type cyclin genes, Cdc25 and E2F1. We demonstrated that c-myc upregulation by the ecdysteroid was not inhibited in the presence of a protein synthesis inhibitor, suggesting a possibility that the ecdysteroid directly stimulates c-myc expression. Finally, results from the administration of a c-Myc inhibitor demonstrated that c-Myc plays an essential role in 20E-inducible cell proliferation. These findings suggested a novel pathway for ecdysteroid-inducible cell proliferation in insects, and it is likely to be conserved between insects and mammals in terms of steroid hormone regulation.
authors.affiliation: Faculty of Agriculture, Utsunomiya University, 350 Mine, Utsunomiya, Tochigi 321-8505, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Moriyama
authors.affiliation: Faculty of Agriculture, Utsunomiya University, 350 Mine, Utsunomiya, Tochigi 321-8505, Japan.
authors.forename: Kohji
authors.initials: K
authors.lastname: Osanai
authors.affiliation: Faculty of Agriculture, Utsunomiya University, 350 Mine, Utsunomiya, Tochigi 321-8505, Japan.
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Ohyoshi
authors.affiliation: Faculty of Agriculture, Utsunomiya University, 350 Mine, Utsunomiya, Tochigi 321-8505, Japan.
authors.forename: Hua-Bing
authors.initials: HB
authors.lastname: Wang
authors.affiliation: Faculty of Agriculture, Utsunomiya University, 350 Mine, Utsunomiya, Tochigi 321-8505, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Iwanaga
authors.affiliation: Faculty of Agriculture, Utsunomiya University, 350 Mine, Utsunomiya, Tochigi 321-8505, Japan. Electronic address: kawasaki@cc.utsunomiya-u.ac.jp.
authors.forename: Hideki
authors.initials: H
authors.lastname: Kawasaki
mesh_terms: D000818:Animals; D012831:Bombyx / Q000254:growth & development*; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000235:genetics; D049109:Cell Proliferation; D026461:Ecdysteroids / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D007814:Larva / Q000254:growth & development; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D014921:Wings, Animal / Q000254:growth & development*
chemical_list: D018797:Cell Cycle Proteins; D026461:Ecdysteroids; D016271:Proto-Oncogene Proteins c-myc
keywords: Cell proliferation; Developmental switching; Ecdysteroid; Silkworm; Wing disc; c-Myc