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

Abstract

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 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 expression and activated expression of tissue inhibitor of metalloproteinases () 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, and, which inhibited expression of the nuclear receptor and competence factor β Moreover, upon a decline in the 20E titer, β expression was induced by the 20E early-late response gene , and then βftz-F1 directly activated expression and inhibited 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.

Juvenile hormone signaling – a mini review

“…In D . melanogaster , a 20‐bp KBS of Kr‐h1 has been identified on the promoter of Mmp1 (matrix metalloproteinase) (Jia et al ., ), in which at least five consecutive bases are conserved with those in B . mori Br and E93 .…”

“…Moreover, the CtC domain of Kr-h1, containing two putative protein interaction motifs (LPPRKR and SVIQFA) might interact with additional corepressors, likely to confer the transcriptional inhibition of Kr-h1 to E93 (Kayukawa et al, 2017). In D. melanogaster, a 20-bp KBS of Kr-h1 has been identified on the promoter of Mmp1 (matrix metalloproteinase) (Jia et al, 2017), in which at least five consecutive bases are conserved with those in B. mori Br and E93.…”

Comparative Transcriptome Analysis Provides Novel Insight into Morphologic and Metabolic Changes in the Fat Body during Silkworm Metamorphosis

“…Morphologically, the larval fat body undergoes tissue dissociation and separates into individual fat cells [ 6 ]. Several genes that respond to the steroid hormone ecdysone, which is involved in the initiation of larval molting and metamorphosis [ 7 , 8 ], have been demonstrated to play key roles in fat body remodeling [ 9 , 10 , 11 ]. For example, in Drosophila , matrix metalloproteinase 1 (Mmp1) and matrix metalloproteinase 2 (Mmp2), two direct targets of the ecdysone-responsive fushi tarazu transcription factor 1(Ftz-f1), promote fat cell dissociation [ 10 , 12 , 13 ].…”

Krüppel homolog 1 represses insect ecdysone biosynthesis by directly inhibiting the transcription of steroidogenic enzymes

“…JH acts together with the Met/Gce receptors to directly induce Kr-h1 expression (15)(16)(17). Importantly, reduction of Kr-h1 activity in the whole body causes precocious metamorphosis (15,18,19), whereas overexpression of Kr-h1 in the Drosophila epidermis or Bombyx whole body disrupts the larval-pupal transition (16,20). In addition, Kr-h1 was also found to negatively regulate ecdysone action by decreasing the expression of ecdysone signaling genes BR-C and E93 in response to JH (21,22).…”