Injury-stimulated and self-restrained BMP signaling dynamically regulates stem cell pool size during Drosophila midgut regeneration

Significance Adult stem cells maintain tissue integrity by producing new cells to replenish damaged cells during tissue homeostasis and in response to injury. Using Drosophila adult midgut as a model we show that midgut injury elicited by chemical feeding or bacterial infection stimulates the production of two bone morphogenetic protein (BMP) ligands (Dpp and Gbb) that are critical for the expansion of the intestinal stem cell (ISC) population and midgut regeneration. Interestingly, we find that BMP expression is inhibited by BMP signaling itself, and this autoinhibition is required for resetting ISC pool size to the homeostatic level after tissue repair. Our study suggests that transient expansion of the stem cell population through the dynamic regulation of niche signals serves as a strategy for regeneration.