TGF-β signaling regulates Drosophila metamorphosis by activating expression of JHAMT, a key regulatory enzyme of juvenile hormone biosynthesis

Juvenile hormone (JH) plays key roles in controlling insect growth and metamorphosis. However, relatively little is known about the regulation of JH biosynthesis. In order to identify genes involved in JH biosynthesis, we designed a novel genetic screen based on precocious expression of broad (br) at early larval stages. Mutations in tkv and mad were isolated that cell-non-autonomously cause precocious br expression. Similar phenotype was observed in dpp mutants. This phenotype could be prevented by an exogenous JH agonist. Targeting expression of mad cDNA to the corpus allatum (CA) was sufficient to suppress precocious br expression in mad mutants. Moreover, mRNA levels and enzymatic activity of JHAMT, a key regulatory enzyme of JH synthesis, was dramatically reduced in Mad-deficient larvae. We conclude that Dpp, Tkv, and Mad-mediated TGF-beta; signaling stimulates JH biosynthesis by activating jhamt transcription in the CA, which in turn prevents premature metamorphosis by repressing br expression at early larval stages..