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

• Published in: eLife Vol. 7
• Main Authors: Cohen, Erez, Allen, Scott R, Sawyer, Jessica K, Fox, Donald T
• Format: Journal Article
• Language: English
• Published: England eLife Science Publications, Ltd 17.08.2018; eLife Sciences Publications Ltd; eLife Sciences Publications, Ltd
• Subjects: Analysis; Animals; Cdh1 Proteins - genetics; Cell cycle; Cell Cycle - genetics; Cell Cycle Proteins - genetics; Cell division; Deoxyribonucleic acid; Developmental Biology; Digestive System - cytology; Digestive System - growth & development; DNA; Drosophila; Drosophila melanogaster - genetics; Drosophila melanogaster - growth & development; Drosophila Proteins - genetics; endocycle; endoreplication; Fruit flies (Tephritidae); Gastric Mucosa - cytology; Gastric Mucosa - growth & development; Gene Expression Regulation, Developmental; Genes; Genetic engineering; Genetic research; Genetically modified organisms; Genomes; Genomics; Growth; Hindgut; Hypertrophy; Insects; Larva - genetics; Larva - growth & development; Liver; Mammals; Mitosis; Mitosis - genetics; Novels; Permeability; Ploidy; Signal Transduction - genetics; Statistical analysis; tissue injury; United States > US; D. melanogaster; tissue injury; developmental biology; endoreplication; endocycle
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.38327

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 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.