Juvenile hormone and BMP signaling modulate fat body cell fate during the transition of previtellogenic development to vitellogenesis

Background: Insect fat body, a central tissue for nutrient storage, energy metabolism, and protein synthesis, degrades by Apoptosis and Autophagy during larval metamorphosis. After adult emergence, the fat body grows rapidly with cell proliferation and polyploidization during the previtellogenic period but ceases cell proliferation in the vitellogenic phase. So far, the regulatory mechanisms underlying fat body cell fate decisions in adulthood remain unknown.

Results: Transcriptomic analysis of locust fat body revealed the enrichment of pathways associated with cell cycle, nuclear division, and DNA replication. Decapentaplegic (Dpp) was among the top of differentially expressed genes in the signaling cascades involved in regulating cell proliferation. Abundance of Dpp, phosphorylated Mad (p-Mad), and Medea increased during the previtellogenic stage and subsequently declined in the vitellogenic phase. Knockdown of Dpp, Mad, and Medea resulted in suppressed fat body cell proliferation, along with remarkably reduced cell number and blocked vitellogenin (Vg) expression in the fat body as well as consequent arrest of egg development. Mad/Medea complex bound to the promoters of cyclin B (CycB) and polo-like kinase 1 (PLK1) and stimulated their expression. Depletion of CycB and PLK1 caused the defective phenotypes resembling Dpp, Mad, and Medea knockdown. In the vitellogenic phase, the high levels of juvenile hormone (JH) promoted the degradation of Medea via fizzy-related protein (Fzr)-mediated ubiquitination, leading to inhibited cell proliferation. The results suggest that fat body cell proliferation in the previtellogenic development is promoted by the bone morphogenetic protein (BMP) signaling pathway, whereas high levels of JH in the vitellogenic stage antagonize BMP signaling for ceasing cell proliferation.

Conclusions: The findings provide novel insights into the regulation of fat body cell fate during the transition of previtellogenic growth to vitellogenic Vg synthesis for reproductive requirements.

BMP signaling; Cell proliferation; Fat body; Female reproduction; Juvenile hormone.