Early signals in Drosophila imaginal disc regeneration : from ROS to Cytokines = Señales tempranas en la regeneración de discos imaginales de Drosophila : desde las ROS hasta las Citoquinas
[eng] Countless environmental aggressors could damage the integrity of tissues and organs. In humans, the limited regenerative ability prevents often the recovery of injured tissues, but this is not the case of the fruit fly Drosophila melanogaster. Drosophila imaginal discs are larval tissues that...
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| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2017 |
| País: | España |
| Institución: | Universidad de Barcelona |
| Repositorio: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/121402 |
| Acceso en línea: | https://hdl.handle.net/2445/121402 http://hdl.handle.net/10803/471539 |
| Access Level: | acceso abierto |
| Palabra clave: | Drosòfila Regeneració (Biologia) Drosophila Regeneration (Biology) |
| Sumario: | [eng] Countless environmental aggressors could damage the integrity of tissues and organs. In humans, the limited regenerative ability prevents often the recovery of injured tissues, but this is not the case of the fruit fly Drosophila melanogaster. Drosophila imaginal discs are larval tissues that can regenerate after fragmentation or massive cell death. That is the reason why in our laboratory, we focused toward the understanding of the genetic basis of imaginal disc repair. We concentrated on the initiation of regeneration, and we found that one of the earliest responses to damage consist in the production of Reactive Oxygen Species (ROS), which propagate from the dying to the nearby living cells, which will drive tissue repair. We revealed that the burst of ROS is essential, because the reduction of those molecules impairs repair. Within the cells, the protein Ask1 (Apoptotic signal-regulating kinase 1) sense ROS and activates both Jun kinase (JNK) and p38 signalling pathways, which are critical for regenerative growth. Although Ask1 was previously associated to apoptosis, we unravelled a novel function related to survival and proliferation. Ask1 inhibition reduces life span after oxidative stress, as well as regenerative ability after cell death. To assume this function, Insulin signalling must attenuate Ask1 activity in living cells. Simultaneously with Ask1, the TNF/Egr signalling acts upstream of JNK after damage, indicating an accurate control of this pathway to promote repair. Finally, we described that both JNK and p38 pathways are necessaries for the transcriptional activation of the cytokines Unpaired, which will promote JAK/STAT signalling to drive regenerative growth and recover the missing tissue. Altogether, we demonstrated a new stress-responsive module composed by many signalling pathways conserved through evolution. Hopefully, in the near future, those findings will help scientists to improve wound healing and regeneration in human tissues and organs. |
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