Fizzy-Related dictates A cell cycle switch during organ repair and tissue growth responses in the Drosophila hindgut

Abstract

Ploidy-increasing cell cycles drive tissue growth in many developing organs. Such cycles, including endocycles, are increasingly appreciated to drive tissue growth following injury or activated growth signaling in mature organs. In these organs, the regulation and distinct roles of different cell cycles remains unclear. Here, we uncover a programmed switch between cell cycles in the Drosophila hindgut pylorus. Using an acute injury model, we identify mitosis as the response in larval pyloric cells, whereas endocycles occur in adult pyloric cells. By developing a novel genetic method, DEMISE (Dual-Expression-Method-for-Induced-Site-specific-Eradication), we show the cell cycle regulator Fizzy-related dictates the decision between mitosis and endocycles. After injury, both cycles accurately restore tissue mass and genome content. However, in response to sustained growth signaling, only endocycles preserve epithelial architecture. Our data reveal distinct cell cycle programming in response to similar stimuli in mature vs. developmental states and reveal a tissue-protective role of endocycles.

Unexpected mutual regulation underlies paralogue functional diversification and promotes maturation of a protective epithelial tissue

“…Differentiation of the serosa involves an early switch from mitosis to the endocycle 29,30 , resulting in polyploidy 13 . Consistent with this, we identified a homologue of the endocycle factor fizzy-related among DE genes upregulated by Tc-Zen1 (Table S1A) 33,34 . From known targets of Tc-Zen1, we also recovered Dorsocross and hindsight, involved in EEM formation 35 , and chitin synthase 1, required for production of the protective cuticle 10 .…”

An abundant quiescent stem cell population inDrosophilaMalpighian tubules protects principal cells from kidney stones

“…Other regions of the gut are maintained and repaired in different ways. The hindgut lacks specialized stem cells and following damage is maintained primarily by induced polyploidization of post-mitotic epithelial cells (Cohen et al, 2018;Fox and Spradling, 2009;Losick et al, 2013;Sawyer et al, 2017).…”

Polyploidy in the adultDrosophilabrain

“…Polyploid cells have the capacity to endure high levels of DNA damage and resist apoptosis. Polyploidisation is also known to respond to tissue damage and play roles in compensatory growth under conditions of cell loss by helping maintain organ size 31,32 and in wound healing by maintaining the integrity of the cuticular epithelium 33,34 .…”