Juvenile hormone acts through FoxO to promote <i>Cdc2</i> and <i>Orc5</i> transcription for polyploidy-dependent vitellogenesis

Abstract

Vitellogenin (Vg) is a prerequisite for egg production and embryonic development after ovipositioning in oviparous animals. In many insects, juvenile hormone (JH) promotes fat body cell polyploidization for the massive Vg synthesis required for the maturation of multiple oocytes, but the underlying mechanisms remain poorly understood. Using the migratory locust <i>Locusta migratoria</i> as a model system, we report here that JH induces the dephosphorylation of Forkhead box O transcription factor (FoxO) through a signaling cascade including leucine carboxyl methyltransferase 1 (LCMT1) and protein phosphatase 2A (PP2A). JH promotes PP2A activity via LCMT1-mediated methylation, consequently triggering FoxO dephosphorylation. Dephosphorylated FoxO binds to the upstream region of two endocycle-related genes, <i>cell-division-cycle 2</i> (<i>Cdc2</i>) and <i>origin-recognition-complex subunit 5</i> (<i>Orc5</i>), and activates their transcription. Depletion of <i>FoxO</i>, <i>Cdc2</i> or <i>Orc5</i> results in blocked polyploidization of fat body cells, accompanied by markedly reduced Vg expression, impaired oocyte maturation and arrested ovarian development. The results suggest that JH acts via LCMT1-PP2A-FoxO to regulate <i>Cdc2</i> and <i>Orc5</i> expression, and to enhance ploidy of fat body cells in preparation for the large-scale Vg synthesis required for synchronous maturation of multiple eggs.