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Back from the 2014 EMBO Conference on The Molecular & Cellular Basis of Regeneration & Tissue Repair held at St. Feliu de Guixols. This was an excellent meeting mainly focussed on basic aspects of regeneration in several animal models. The role of ROS signalling and the inflammatory response on wound healing and the triggering of a regenerative response were some of the hottest topics of the meeting, as well as neural and heart regeneration. Also, there were some talks and posters on new (or not so popular yet) models for regeneration such as the cnidarian Nematostella vectensis, several echinoderms and the crustacean Parhyale hawaiensis. It is also clear that large transcriptomic analyses and the enormous amount of data currently generated from RNAseq experiments in all different models and regenerative contexts will help to identify the molecular and cellular bases of key events of regeneration such us wound healing, blastema formation and growth, patterning and polarity, among others. Thus, comparative analyses might uncover novel conserved and taxon-specific elements required for regeneration. I hope we can discuss all this data in the near future in this blog.
Just a short notice to inform you that I am going to take some weeks off for summer break. I will back in September to continue posting about regeneration. The beginning of September will be also an exciting time as there will be the EMBO Conference on Regeneration in Sant Feliu de Guixols (near Barcelona), so I hope we can learn a lot from the data presented there.
Have a nice summer!
Wound healing is a universal response to injury conserved in all animals. However, not in all cases wound healing is followed by a successful functional regeneration. Thus, for example, skin injuries in adult mammals are usually solved through a so-called scarring wound healing that does not allow a functional recovery of the damaged skin. On the other side, in regeneration-competent species wound healing does not a have a negative effect but on the contrary is a key first step to trigger a regenerative response. Thus, in those cases, impairing wound healing results in the inhibition of regeneration. A deep characterization of the cellular and molecular events that result in scarring or regenerative wound healing may be very important to try to develop strategies and therapies to enhance the poor regenerative abilities shown by many animals. Now, a recent paper from the laboratory of Mark Martindale has characterized the regenerative wound healing in the cnidarian Nematostella vectensis (http://www.ncbi.nlm.nih.gov/pubmed/24670243).
In a first set of experiments the authors characterized the cellular and molecular events that occurred after injuring the animals by making punctures in their bodies with a glass needle. Two hours after injury an enrichment of actin was seen around the injury site and the wounds were healed after 6 hours. In another cnidarian, Hydra, and some vertebrates, apoptosis is required to trigger a proliferative response that leads to a successful regeneration. Similarly, upon injury along the ectodermal surface of Nematostella, apoptosis was significantly upregulated. Next, the authors decided to conduct a pharmacological screen to see which signaling pathways could have a role in wound healing and regeneration in these animals. Inhibition of the Notch pathway blocked head regeneration without affecting wound healing. On the other side, and unexpectedly, they did not found any defect after blocking the TGFB signaling. Finally, they inhibited ERK signaling and found a strong impairment of wound healing and regeneration. The MAPK signaling pathway plays many functions including immune response, cell proliferation, apoptosis and cell movement. In Drosophila, ERK (through MAPK) regulates actin dynamics at the injury site a the early stages of wound healing. Using their puncture assay they found that inhibiting ERK signaling with the drug U0126 caused wound to remain open after six hours and also eliminated the local phosphorylation of ERK at one hour after injury, compared to the wound response of untreated animals. U0216 did not blocked the initial apoptotic response to injury indicating that apoptosis by itself is not sufficient to trigger a regenerative response. Also, the animals treated with U0216 did not show much actin concentration around the injury suggesting that ERK could be targeting cell movement and adhesion.
Then, the authors used Nematostella genome-wide microarrays to identify genes involved in wound healing. They analyzed the gene profiles from samples taken 1 hour and 4 hours after injury in untreated and U0216 treated animals, which allowed them to do many comparisons. Thus, they generated a profile of genes not only up- or down-regulated at early (1h) and late (4h) stages of normal wound healing, but also how the expression of those genes was affected after inhibiting the ERK pathway. After injury and wound healing genes upregulated included genes with peptidase activity, modulators of MAPK signaling, Sox E1 and runt transcription factors, growth factor-related genes as well as genes related to mucus proteins. Some of these genes were validated by qPCR and/or in situ hybridizations. The authors focused then in several genes: uromodulin, soxE, thiamine enzyme, a matrix metalloproteinase (MMP) inhibitor and a maltase-like gene. In all cases these genes were upregulated upon injury and this upregulation appeared dependent of ERK signaling, as it was not observed after treatment with U0216. Remarkably, all these genes were upregulated during regeneration after amputation through the oral-aboral axis. Again, the expression of these genes during regeneration was dependent of ERK signaling.
To conclude, the authors propose that ERK signaling would be necessary for the initiation of the early wound healing response in Nematostella, agreeing with the important functions of the ERK signaling during regeneration reported in other systems. Future functional analyses on the genes identified here should help to confirm this hypothesis and to better characterize wound healing at the gene expression level. In summary, this is the first report of genes involved in wound healing in Nematostella. Comparisons of the cellular and molecular events that characterize Nematostella wound healing with those found in other regenerative models as well as in regeneration-incompetent animals could help to understand better this key initial process that takes place after any injury.
Just one year ago I started this blog on regeneration in nature. After 20 years working on planarian regeneration (since I was an undergraduate in 1993), writing papers, attending to meetings and fulfilling my academic obligations (at both levels, teaching and administrative, that since 2006) I felt myself with the need to do something different. The idea of writing a blog had been in my mind since long ago; however, I was undecided on what to write about: science, politics, social issues or personal thoughts (whatever that means). At the end, I decided to write about regeneration because on one side, the study of regeneration has made me a scientist and, on the other, it has offered me the opportunity to go through important vital experiences such as living in Okayama (Japan) and Urbana (USA) which have influenced somehow how I am nowadays. So, in many aspects, and as it happens to most of us, what we do influences on how we are and, the other way around, how we are influences on what we do. And at some point it is difficult to establish what is a cause and what is a consequence. Therefore, I felt in debt with regeneration so I decided to start this blog to share my passion for this biological phenomenon with as many people as possible. One year later I feel really happy with this blog. As many of you know I post my comments on Thursdays and I must say that many weeks I am really eager that that day arrives.
But a blog is nothing without its readers so I would really like to thank all of you that regularly visit this blog (80 people are already subscribed and therefore receive an automatic e-mail every time a new post is published) or just hit it by chance and stay few minutes reading some of the posts. And I really appreciate readers such as Oné Pagan (follow his blog at http://baldscientist.wordpress.com) and Jaume Baguñà for their often comments to my posts. I hope that you keep visiting this blog, enjoying the posts, learning about regeneration and, if you have few minutes do not be shy and just comment on any of the posts you like or you do not like. It is only with your help and implication that this blog can become a two-direction or multi-direction communication and discussion channel.
Here you can see some stats of the 12,383 views that this blog has had during its first year.
Thank you very much again and as Oné often says in his blog: “Stay tuned”.