Intrinsic and damage-induced JAK/STAT signaling regulate developmental timing by the Drosophila prothoracic gland

Abstract

Development involves tightly paced, reproducible sequences of events, yet it must adjust to conditions external to it, such as resource availability and organismal damage. A major mediator of damage-induced immune responses in vertebrates and insects is JAK/STAT signaling. At the same time, JAK/STAT activation by the Drosophila Upd cytokines is pleiotropically involved in normal development of multiple organs. Whether inflammatory and developmental roles of JAK/STAT intersect is unknown. Here, we show that JAK/STAT is active during development of the prothoracic gland (PG), the organ that controls metamorphosis onset through ecdysone production. Reducing JAK/STAT signaling decreased PG size and slightly advanced metamorphosis. Conversely, JAK/STAT hyperactivation, achieved through overexpression of pathway components or SUMOylation loss, caused PG hypertrophy and metamorphosis delay. Interestingly, tissue damage and tumors, known to secrete Upd cytokines, also activated JAK/STAT in the PG and delayed metamorphosis. Finally, we show that expression of transcription factor Apontic, a JAK/STAT target in the PG, recapitulates PG hypertrophy and metamorphosis delay. JAK/STAT damage signaling, therefore, regulates metamorphosis onset at least in part by coopting its developmental role in the PG.

The wing imaginal disc

“…While regulation of Dilp8 can occur in other imaginal discs, most studies of Dilp8 have focused on wing discs, which presumably have a key role in Dilp8 regulation as the largest of the imaginal discs. Other signals secreted by imaginal discs, including Dpp and Upd3, can also influence ecdysone production ( Setiawan et al 2018 ; Cao et al 2021 ; Romão et al 2021 ). Dpp pathway activation in the prothoracic gland declines in older larvae, suggesting that, as for Dilp8, levels of Dpp released by imaginal discs may help coordinate growth and developmental transitions ( Setiawan et al 2018 ).…”

“…Expression of Dilp8 is promoted by multiple pathways upregulated during regeneration, including Jnk, Yki, and Jak-Stat ( Colombani et al 2012 ; Katsuyama et al 2015 ; Boone et al 2016 ). In addition to regulating Dilp8, Upd3 cytokines secreted by regenerating or tumorous larval tissues can also act directly on the prothoracic gland to suppress ecdysone production ( Cao et al 2021 ; Romão et al 2021 ).…”