Biology subjects

Serras, F.

Publications and source records attributed to Serras, F..

5 recordsLinked to original sources

bioRxiv2026

Oxidative inhibition of PTEN links ROS signaling to regeneration and homeostasis

Reactive oxygen species (ROS) are early signals of tissue damage, but how they engage growth-promoting pathways in vivo is unclear. Here we show that ROS promote regeneration by inhibiting PTEN, thereby activating PI3K-Akt signaling in Drosophila melanogaster. We identify cysteine 79 as an essential residue for redox regulation of PTEN, demonstrating that a ROS-insensitive PTEN mutant uncouples Akt activation from oxidative stress. This disruption impairs regenerative growth in wing imaginal epithelia and stem cell proliferation in the adult gut. Mechanistically, Akt activation links ROS signaling to p38 MAPK-dependent regeneration responses. Together, our findings define a conserved ROS-PTEN-Akt signaling axis that integrates oxidative damage with regenerative growth, establishing PTEN as a key redox-sensitive regulator of tissue repair.

developmental biology↗

bioRxiv2024

Gill regeneration in the mayfly Cloeon uncovers new molecular pathways in insect regeneration

The capacity to regenerate lost or damaged organs is widespread among animals, and yet, the species in which regeneration has been experimentally probed using molecular and functional assays is very small. This is also the case for insects, for which we still lack a complete picture of their regeneration mechanisms and the extent of conservation of these mechanisms. Here we contribute to filling this gap by investigating regeneration in the mayfly Cloeon dipterum. Mayflies, or Ephemeroptera, appeared early in the evolution of insects. We focus on the abdominal gills of Cloeon nymphs, which are critical for osmoregulation and gas exchange. After amputation, gills re-grow faster than they do during normal development. Direct cell count and EdU proliferation assays indicate that growth acceleration involves an uniform increase in cell proliferation throughout the gill, rather than a localized growth zone. Transcriptomic analysis reveals an early enrichment in cell cycle-related genes, in agreement with fast proliferation. Several other gene classes are also enriched in regenerating gills, including protein neddylation and other proteostatic processes. We then showed that protein neddylation, the activin signaling pathway or the mRNA-binding protein Lin28, among other genes and processes, are required for Drosophila larval/pupal wing regeneration, and that some of these genes may have a regeneration-specific function in the wing. Globally, our results contribute to elucidating regeneration mechanisms in mayflies and suggest a conservation of regeneration mechanisms across insects, as evidenced by the regenerative role of candidate genes identified in Cloeon in the distant Drosophila.

developmental biology↗

bioRxiv2024

Expression dynamics of long non-coding RNAs during imaginal disc development and regeneration in Drosophila

The discovery of functional long non-coding RNAs (lncRNAs) changed their initial concept as transcriptional noise. LncRNAs have been found to participate in the regulation of multiple biological processes, including chromatin structure, gene expression, splicing, and mRNA degradation and translation. However, functional studies of lncRNAs are hindered by the usual lack of phenotypes upon deletion or inhibition. Here, we used Drosophila imaginal discs as a model system to identify lncRNAs involved in development and regeneration. We examined a subset of lncRNAs expressed in the wing, leg, and eye disc development. Additionally, we analyzed transcriptomic data from regenerating wing discs to profile the expression pattern of lncRNAs during tissue repair. We focused on the lncRNA CR40469, which is upregulated during regeneration. We generated CR40469 mutant flies that developed normally but showed impaired wing regeneration upon the induction of cell death. The ability of these mutants to regenerate was restored by the ectopic expression of CR40469. Furthermore, we found that the lncRNA CR34335 has a high degree of sequence similarity with CR40469 and can partially compensate for its function during regeneration in the absence of CR40469. Our findings point to a potential role of the lncRNA CR40469 in trans during the response to damage in the wing imaginal disc.

developmental biology↗

bioRxiv2023

ROS-mediated TNFR Wengen activation in response to apoptosis

The activation of tumor necrosis factor receptors (TNFR) controls pleiotropic pro-inflammatory functions ranging from apoptosis to survival. The ability to trigger a particular function will depend on the upstream activation, association with regulatory complexes and downstream pathways. In Drosophila, two TNFRs have been identified, Wengen (Wgn) and Grindelwald (Grnd). Although several reports associate these receptors with JNK-dependent apoptosis, it has recently been found that Wgn activates a variety of functions. We demonstrate that Wgn is required for survival by protecting cells from apoptosis. This is mediated by the signaling molecule dTRAF1 and results in the activation of the p38 MAP kinase signaling pathway. Remarkably, Wgn is required for apoptosis-induced regeneration and is activated by the reactive oxygen species (ROS) produced following apoptosis. This ROS activation is exclusive for Wgn, but not for Grnd, and occurs in the absence of the ligand Eiger/TNF. Furthermore, based on protein sequence conservation, the extracellular Cys-rich domain of Grnd is much more divergent and phylogenetically restricted than that of Wgn, which is more similar to TNFR families from other animals, including those of human TNFRs. Taken together, our results show a novel function for a TNFR that responds to cellular damage by ensuring the cell survival required for the response to damage.

developmental biology↗

bioRxiv2018

Ask1 and Akt act synergistically to promote ROS-dependent regeneration in Drosophila

The mechanism by which apoptotic cells release signals that induce undamaged neighbor cells to proliferate and regenerate missing parts remains elusive. Oxidative stress originated by dying or damaged cells can be propagated to neighboring cells, which then promote regeneration. We investigated the nature of the stress sensing mechanism by which neighboring cells are recruited. We found that Drosophila apoptosis signal-regulating kinase 1 (Ask1) senses reactive oxygen species (ROS) differently in stressed dying cells and unstressed neighboring cells and this differential sensing is pivotal for tissue repair. In undamaged cells, this activity is attenuated, but not abolished, by Akt1 phosphorylation, which thus acts as a survival signal that results in the tolerable levels of p38 and JNK necessary for regeneration. These observations demonstrate that the non-autonomous activation of the ROS-sensing mechanism by Ask1 and Akt1 in neighboring unstressed cells. Collectively, these results provide the basis for understanding the molecular mechanism of communication between dying and living cells that triggers regeneration.\n\nAuthor summaryOne of the early events that occur after tissue damage is oxidative stress production that signals to initiate wound healing and regeneration. Several signaling pathways, such as JNK and p38, respond to oxidative stress and are necessary for regeneration. We decided to explore the mechanism that links the oxidative stress and the activation of these pathways. We used epithelia of Drosophila to genetically direct cell death in specific zones of the tissue as means of experimentally controlled cell damage. We found that the Ask1 protein, which is sensitive to oxidative stress, is a key player in this scenario. Actually it acts as an intracellular sensor that upon damage activates those signaling pathways. However, high activity of Ask1 can be toxic for the cell. This is controlled by Akt, an enzyme dowstream the insulin pathway, with attenuates the activity of Ask1 to tolerable levels. In conclusion, Ask1 and Akt act synergistically to respond to the stress generated after tissue damage and drive regeneration. In other words, we found that the link between oxidative stress and nutrition is key for tissue regeneration.

developmental biology↗