TGF-β signaling in insects regulates metamorphosis via juvenile hormone biosynthesis

While butterflies undergo a dramatic morphological transformation from larvae to adult via a pupal stage (e.g., holometamorphosis), crickets undergo a metamorphosis from nymph to adult without formation of a pupa (e.g., hemimetamorphosis). Despite these differences, both processes are regulated by common mechanisms that involve 20-hydroxyecdysone (20E) and juvenile hormone (JH). JH regulates many aspects of insect physiology, such as development, reproduction, diapauses, and metamorphosis. Consequently, strict regulation of JH levels is crucial throughout an insect’s life cycle. However, it remains unclear how JH synthesis is regulated. Here, we report that in the corpora allata (CA) of the cricket, Gryllus bimaculatus (Gb), Myoglianin (Gb’Myo), a homolog of Drosophila Myoglianin/vertebrate GDF8/11, is involved in the down-regulation of JH production by suppressing expression of a gene encoding JH acid O-methyltransferase, Gb’jhamt. In contrast, JH production is up-regulated by Decapentaplegic (Gb’Dpp) and Glass bottom boat/60A (Gb’Gbb) signaling that occurs as part of the transcriptional activation of Gb’jhamt. Gb’Myo defines the nature of each developmental transition by regulating JH titre and the interactions between JH and 20E. When Gb’myo expression is suppressed, activation of Gb’jhamt expression and secretion of 20E induces molting, thereby leading to the next instar prior to the last nymphal instar. Conversely, high Gb’myo expression induces metamorphosis during the last nymphal instar due to cessation of JH synthesis. Gb’myo also regulates final insect size. Since Myoglianin/GDF8/11 and Dpp/BMP2/4-Gbb/BMP5-8 are conserved in both invertebrates and vertebrates, the present findings provide common regulatory mechanisms regarding endocrine control of animal development.