Juvenile hormone and 20-hydroxyecdysone coordinately control the developmental timing of matrix metalloproteinase-induced fat body cell dissociation.

Tissue remodeling is a crucial process in animal development and disease progression. Coordinately controlled by the two main insect hormones, juvenile hormone (JH) and 20-hydroxyecdysone (20E), tissues are remodeled context-specifically during insect metamorphosis. We previously discovered that two matrix metalloproteinases (Mmps) cooperatively induce fat body cell dissociation in Drosophila However, the molecular events involved in this Mmp-mediated dissociation are unclear. Here we report that JH and 20E coordinately and precisely control the developmental timing of Mmp-induced fat body cell dissociation. We found that during the larval-prepupal transition, the anti-metamorphic factor Kr-h1 transduces JH signaling, which directly inhibited Mmp expression and activated expression of tissue inhibitor of metalloproteinases (timp) and thereby suppressed Mmp-induced fat body cell dissociation. We also noted that upon a decline in the JH titer, a prepupal peak of 20E suppresses Mmp-induced fat body cell dissociation through the 20E primary-response genes, E75 and Blimp-1, which inhibited expression of the nuclear receptor and competence factor βftz-F1 Moreover, upon a decline in the 20E titer, βftz-F1 expression was induced by the 20E early-late response gene DHR3, and then βftz-F1 directly activated Mmp expression and inhibited timp expression, causing Mmp-induced fat body cell dissociation during 6-12 h after puparium formation. In conclusion, coordinated signaling via JH and 20E finely tunes the developmental timing of Mmp-induced fat body cell dissociation. Our findings shed critical light on hormonal regulation of insect metamorphosis.