Hormone Signaling Synchronizes Regeneration with Development Progression

In multicellular organisms, hormones are a critical part of growth coordination between tissues and the whole organism. Systemic hormone signaling acts as a timer that ensures the developmental progression of all tissues is coordinated. This coordination is lost when tissues are injured, and the damaged tissues need to be repaired and catch up with the development of undamaged tissues. How do the organisms reestablish the coordination? In Drosophila imaginal disc regeneration, growth coordination is reestablished by decreasing systemic levels of the steroid hormone ecdysone, a key coordinator of their developmental progression. At the end of larval development, an increase in systemic levels of ecdysone initiates pupation and causes a loss of regenerative capacity. Regenerating imaginal discs release the relaxin hormone Dilp8, limiting ecdysone synthesis and extending the regenerative period, allowing the damaged tissue time to repair and catch up.

However, during my thesis research, I observed that dilp8- mutants can still regenerate their wing discs despite the lack of regenerative checkpoint delay following damage. I established that ecdysone coordinates regeneration with developmental progression, even as its levels are limited during regeneration. Here, I describe how regenerating tissues produce a biphasic response to ecdysone levels: lower concentrations promote local and systemic regenerative signaling, whereas higher concentrations suppress regeneration via the expression of broad splice isoforms. This dual role for ecdysone explains how regeneration is completed in dilp8- mutants: their higher ecdysone levels increase the regenerative activity, allowing regeneration completion in a shorter timeframe. However, completion of regeneration within a limited time comes at the cost of pupal viability.