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

• Published in: The Journal of biological chemistry 2017-12, Vol.292 (52), p.21504-21516
• Main Authors: Jia, Qiangqiang, Liu, Suning, Wen, Di, Cheng, Yongxu, Bendena, William G., Wang, Jian, Li, Sheng
• Format: Article
• Language: English
• Subjects: 20-hydroxyecdysone; Animals; cell dissociation; development; Developmental Biology; Drosophila melanogaster - genetics; Drosophila melanogaster - metabolism; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; Ecdysterone - metabolism; Ecdysterone - physiology; fat body; Fat Body - metabolism; Fat Body - physiology; Gene Expression Regulation, Developmental - drug effects; Gene Expression Regulation, Developmental - genetics; juvenile hormone (JH); Juvenile Hormones - metabolism; Juvenile Hormones - physiology; Kruppel-Like Transcription Factors - metabolism; Larva - growth & development; matrix metalloproteinase (Mmp); Matrix Metalloproteinases - genetics; Matrix Metalloproteinases - metabolism; Metamorphosis, Biological - drug effects; Metamorphosis, Biological - physiology; signal transduction; Signal Transduction - drug effects; steroid hormone; Tissue Inhibitor of Metalloproteinases - metabolism; Transcription Factors - metabolism; Transcription, Genetic - drug effects
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M117.818880

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.