Halme, A. | bioRxiv Science

bioRxiv2021

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

In Drosophila melanogaster, loss of regenerative capacity in wing imaginal discs coincides with an increase in systemic levels of the steroid hormone ecdysone, a key coordinator of their developmental progression. Regenerating discs release the relaxin hormone Dilp8, which limits ecdysone synthesis and extends the regenerative period. Here, we describe how regenerating tissues produce a biphasic response to ecdysone levels: lower concentrations of ecdysone promote local and systemic regenerative signaling, whereas higher concentrations suppress regeneration through the expression of broad splice isoforms. Ecdysone also promotes the expression of wingless during both regeneration and normal development through a distinct regulatory pathway. This dual role for ecdysone explains how regeneration can still be completed successfully in dilp8- mutant larvae: higher ecdysone levels increase the regenerative activity of tissues, allowing regeneration to reach completion in a shorter time. From these observations, we propose that ecdysone hormone signaling functions to coordinate regeneration with developmental progression. Summary StatementEcdysone coordinates regenerative activity with developmental progression through the biphasic, concentration-dependent activation, and suppression of regenerative signaling.

developmental biology↗

bioRxiv2020

Ecdysone regulates the Drosophila imaginal disc epithelial barrier, determining the duration of regeneration checkpoint delay

Regeneration of Drosophila imaginal discs, larval precursors to adult tissues, produces a systemic response, a regeneration checkpoint that coordinates regenerative growth with developmental progression. This regeneration checkpoint is coordinated by the release of the relaxin-family peptide Dilp8 from regenerating tissues. Secreted Dilp8 protein can be detected within the imaginal disc lumen. The disc epithelium separates from the lumen from the larval hemolymph and the targets for Dilp8 activity in the brain and prothoracic gland. Here we demonstrate that the imaginal disc epithelial barrier limits Dilp8 signaling and checkpoint delay. We also observe that the wing imaginal disc barrier becomes more restrictive during development, becoming impermeable only at end of the final larval instar. This change in barrier permeability is driven by the steroid hormone ecdysone and correlates with changes in localization of Coracle, a component of the septate junctions that is required for the late, impermeable epithelial barrier. Based on these observations, we propose that the imaginal disc epithelial barrier regulates the duration of the regenerative checkpoint, providing a mechanism by which tissue function can signal the completion of regeneration. Summary StatementEcdysone signaling directs the Drosophila third instar imaginal disc epithelial barrier to mature, becoming more restrictive. This mature barrier limits Dilp8 signaling and determines the duration of the regeneration checkpoint.

developmental biology↗