PLoS genetics, 2019-08, Vol.15 (8), p.e1008133-e1008133
2019
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- Autor(en) / Beteiligte
- Titel
- Eiger/TNFα-mediated Dilp8 and ROS production coordinate intra-organ growth in Drosophila
- Ist Teil von
- PLoS genetics, 2019-08, Vol.15 (8), p.e1008133-e1008133
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2019
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Coordinated intra- and inter-organ growth during animal development is essential to ensure a correctly proportioned individual. The Drosophila wing has been a valuable model system to reveal the existence of a stress response mechanism involved in the coordination of growth between adjacent cell populations and to identify a role of the fly orthologue of p53 (Dmp53) in this process. Here we identify the molecular mechanisms used by Dmp53 to regulate growth and proliferation in a non-autonomous manner. First, Dmp53-mediated transcriptional induction of Eiger, the fly orthologue of TNFα ligand, leads to the cell-autonomous activation of JNK. Second, two distinct signaling events downstream of the Eiger/JNK axis are induced in order to independently regulate tissue size and cell number in adjacent cell populations. Whereas expression of the hormone dILP8 acts systemically to reduce growth rates and tissue size of adjacent cell populations, the production of Reactive Oxygen Species-downstream of Eiger/JNK and as a consequence of apoptosis induction-acts in a non-cell-autonomous manner to reduce proliferation rates. Our results unravel how local and systemic signals act concertedly within a tissue to coordinate growth and proliferation, thereby generating well-proportioned organs and functionally integrated adults.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1553-7404, 1553-7390eISSN: 1553-7404DOI: 10.1371/journal.pgen.1008133Titel-ID: cdi_plos_journals_2291478908
- Format
- –
- Schlagworte
- Animals, Animals, Genetically Modified, Apoptosis, Apoptosis - genetics, Biology and Life Sciences, Cell activation, Cell cycle, Cell growth, Cell number, Cell Proliferation - genetics, Cell size, Cellular stress response, Drosophila, Drosophila melanogaster - physiology, Drosophila Proteins - genetics, Drosophila Proteins - metabolism, Fibroblasts, Gene Expression Regulation, Developmental, Growth rate, Homeostasis, Insects, Intercellular Signaling Peptides and Proteins - genetics, Intercellular Signaling Peptides and Proteins - metabolism, Kinases, Larva - growth & development, MAP Kinase Signaling System - genetics, Medicine and Health Sciences, Membrane Proteins - genetics, Membrane Proteins - metabolism, Menopause, Models, Animal, Molecular modelling, Organ Size - genetics, p53 Protein, Reactive oxygen species, Reactive Oxygen Species - metabolism, Research and Analysis Methods, Signal transduction, Transcription, Tumor necrosis factor-α, Tumor Suppressor Protein p53 - metabolism, Tumorigenesis, Wings, Animal - growth & development