The Drosophila Duox maturation factor is a key component of a positive feedback loop that sustains regeneration signaling
| Autor: | Andrea Skinner, Syeda Nayab Fatima Abidi, Sumbul Jawed Khan, Yuan Tian, Rachel K. Smith-Bolton |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cancer Research Cell signaling MAP Kinase Kinase 4 Mutant Gene Expression Signal transduction Biochemistry Epithelium Oxidative Damage Gene expression Transcriptional regulation Morphogenesis Medicine and Health Sciences Drosophila Proteins Wings Animal Genetics (clinical) Genetics Regulation of gene expression biology Drosophila Melanogaster Signaling cascades Gene Expression Regulation Developmental Animal Models c-Jun N-terminal kinase signaling cascade Cell biology Insects Imaginal disc Imaginal Discs Experimental Organism Systems Drosophila Drosophila melanogaster Anatomy Blastema Research Article lcsh:QH426-470 Arthropoda MAP Kinase Signaling System Research and Analysis Methods 03 medical and health sciences Model Organisms Regeneration Animals Gene Regulation Molecular Biology Ecology Evolution Behavior and Systematics Positive feedback Body Patterning Cell Proliferation Organisms Biology and Life Sciences biology.organism_classification Invertebrates lcsh:Genetics 030104 developmental biology Biological Tissue Reactive Oxygen Species Carrier Proteins Organism Development Developmental Biology |
| Zdroj: | PLoS Genetics PLoS Genetics, Vol 13, Iss 7, p e1006937 (2017) |
| ISSN: | 1553-7404 1553-7390 |
| Popis: | Regenerating tissue must initiate the signaling that drives regenerative growth, and sustain that signaling long enough for regeneration to complete. How these key signals are sustained is unclear. To gain a comprehensive view of the changes in gene expression that occur during regeneration, we performed whole-genome mRNAseq of actively regenerating tissue from damaged Drosophila wing imaginal discs. We used genetic tools to ablate the wing primordium to induce regeneration, and carried out transcriptional profiling of the regeneration blastema by fluorescently labeling and sorting the blastema cells, thus identifying differentially expressed genes. Importantly, by using genetic mutants of several of these differentially expressed genes we have confirmed that they have roles in regeneration. Using this approach, we show that high expression of the gene moladietz (mol), which encodes the Duox-maturation factor NIP, is required during regeneration to produce reactive oxygen species (ROS), which in turn sustain JNK signaling during regeneration. We also show that JNK signaling upregulates mol expression, thereby activating a positive feedback signal that ensures the prolonged JNK activation required for regenerative growth. Thus, by whole-genome transcriptional profiling of regenerating tissue we have identified a positive feedback loop that regulates the extent of regenerative growth. Author summary Regenerating tissue must initiate the signaling that drives regenerative growth, and then sustain that signaling long enough for regeneration to complete. Drosophila imaginal discs, the epithelial structures in the larva that will form the adult animal during metamorphosis, have been an important model system for tissue repair and regeneration for over 60 years. Here we show that damage-induced JNK signaling leads to the upregulation of a gene called moladietz, which encodes a co-factor for an enzyme, NADPH dual oxidase (Duox), that generates reactive oxygen species (ROS), a key tissue-damage signal. High expression of moladietz induces continuous production of ROS in the regenerating tissue. The sustained production of ROS then continues to activate JNK signaling throughout the course of regeneration, ensuring maximal tissue regrowth. |
| Databáze: | OpenAIRE |
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