CtBP impedes JNK- and Upd/STAT-driven cell fate misspecifications in regenerating Drosophila imaginal discs

• DOI: 10.7554/elife.30391
• Publication Date: 2018-01-26T13:00:07Z
• Authors: Melanie I Worley; Larissa A Alexander; Iswar K Hariharan
• Keywords: 0301 basic medicine; Biomedical and clinical sciences; QH301-705.5; MAP Kinase Kinase 4; 1.1 Normal biological development and functioning; Science; 610; Regenerative Medicine; developmental biology; 03 medical and health sciences; Underpinning research; stem cells; transdetermination; Genetics; Animals; Drosophila Proteins; tissue repair; Biology (General); D. melanogaster; Q; R; Health sciences; Cell Differentiation; Biological Sciences; Stem Cells and Regenerative Medicine; DNA-Binding Proteins; Biological sciences; Alcohol Oxidoreductases; STAT Transcription Factors; Gene Expression Regulation; Imaginal Discs; regeneration; plasticity; Medicine; Drosophila; Biochemistry and Cell Biology; Generic health relevance; Transcription Factors

Regeneration following tissue damage often necessitates a mechanism for cellular re-programming, so that surviving cells can give rise to all cell types originally found in the damaged tissue. This process, if unchecked, can also generate cell types that are inappropriate for a given location. We conducted a screen for genes that negatively regulate the frequency of notum-to-wing transformations following genetic ablation and regeneration of the wing pouch, from which we identified mutations in the transcriptional co-repressor C-terminal Binding Protein (CtBP). When CtBP function is reduced, ablation of the pouch can activate the JNK/AP-1 and JAK/STAT pathways in the notum to destabilize cell fates. Ectopic expression of Wingless and Dilp8 precede the formation of the ectopic pouch, which is subsequently generated by recruitment of both anterior and posterior cells near the compartment boundary. Thus, CtBP stabilizes cell fates following damage by opposing the destabilizing effects of the JNK/AP-1 and JAK/STAT pathways.