Ecdysone exerts biphasic control of regenerative signaling, coordinating the completion of regeneration with developmental progression

Abstract

Significance For most organisms, regenerative capacity varies at different stages of development. Changes in regenerative capacity often correlate with significant changes in systemic hormone signaling. Previous studies have independently demonstrated the positive and negative effects of systemic hormone signals on the regenerative activity of tissues. Here, we report that regenerating Drosophila melanogaster tissues produce a biphasic response to ecdysone steroid hormone levels. Below a certain threshold, ecdysone promotes regenerative activity in damaged imaginal discs. As development progresses, ecdysone levels increase above this threshold and suppress regeneration via the sequential expression of Broad transcription factor splice isoforms. Our findings describe how systemic hormone signals can direct regenerative activity to coordinate regeneration completion with developmental transitions.