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Evolution of regeneration in spiralians

One of the on-going debates in the regeneration field concerns how the regenerative capabilities shown by different animal groups have evolved. When considering the animal phylogeny we can see how most phyla contain species capable of regenerating. However, a huge variability exists in: 1) the regeneration power shown by closely related species and 2) the biological level of regeneration as depending on the model they can regenerate only specific cell types, or some tissues and/or organs, or structures and complex parts (for example, a limb) or, finally, the real champions capable of regenerating the whole body.

A recent paper by Alexandra Bely and colleagues discusses about the evolution of regeneration, especially within the spiralians ( As the authors raise, an important question is whether regeneration variation among bilaterians is the results of regeneration losses, independent gains or a combination of both. That is, was regeneration a feature that was already present in the last common ancestor of all bilaterians and has been lost in some taxonomic groups? or, alternatively, is something that has independently appeared in some groups and not others?

In order to address these questions it is absolutely necessary to gather as much information as possible about the regeneration capabilities of as many animal groups as possible and, more importantly, characterize the cellular and molecular processes that guide regeneration in those animals. Also, it is important to understand why very closely related species can differ significantly in their regenerative capabilities. In this review, the authors focussed on the Spiralia, a large and diverse protostome clade composed of 13 phyla including annelids, molluscs, nemerteans, platyhelminthes and rotifers. Importantly, there is an important variability of regeneration not only between different spiralian phyla but also within them.

Thus, annelids include species that can regenerate every part of the body, including some that can regenerate a whole animal from a single body segment, as well as species totally incapable of regenerating a single segment lost. In general, the capacity to regenerate posterior segments is very broadly distributed within the phylum. In contrast, the ability to regenerate anterior segments is much more variable and, in fact, the failure to regenerate anterior segments has been shown in over a third of the families from which data are available. Nemerteans can undergo growth and degrowth indicating processes of remodelling. Some animals can be maintained starved for over a year shrinking in size but otherwise apparently happy. Among them, regeneration of the proboscis (used for prey capture), tail and head occurs in some groups, and some species can regenerate the whole animal from a tiny body piece. Posterior regeneration is not in general very well documented because the lack of easily scorable structures. Anterior regeneration appears to be very limited within this group although some species of one particular family can regenerate a complete head. However, this seems to be an exception within this phylum, which could imply that it might be a regeneration gain of this particular family.

Among Platyhelminthes, the triclads (planarians) are the best known in terms of their regenerative capabilities. However, it is also true that a number of groups of this phylum have much more limited regenerative capacities. Also, within this phylum posterior regeneration appears to be more widespread than anterior regeneration. Finally, within molluscs we do not have any representative capable of regenerating the whole body. However, different species can regenerate specific structures such as the foot, anterior neural elements, tentacles and even the entire head in some gastropods.

Next, the authors review what is known about the cellular and molecular basis of regeneration within these different phyla. Thus, in annelids after amputation there is a rapid muscle contraction to seal the wound. During the very first stages of wound healing and regeneration, proliferation throughout most of the body seems to be shut down. At the same time there is a large cell migration response towards the wound. After wound healing, cells near the wound start proliferating forming a regenerative blastema. The origin of the regenerative cells within the blastema seems to come from the proliferation of the three tissue layers close to the wound. The role of annelid neoblasts (undifferentiated cells) in regeneration is still under debate. Also, several genes have been shown to be expressed within the blastema including markers of stem cells and germline as well as Hox genes. Interestingly, all these genes expressed within the blastema are also detected during normal growth in the posterior growth zone. This suggests a shared molecular mechanism between regeneration and growth. Finally, regeneration does not uniquely imply the formation of new tissues and structures but also a remodelling of the pre-existing tissues.

In nemerteans, amputation is followed by muscle contraction and wound healing followed by a phase of cell proliferation and the formation of a regenerative blastema, much more evident during anterior regeneration than in posterior regenerates. Unfortunately, the origin of the regenerative cells of the blastema is obscure, and although some old studies pointed to the role of some putative undifferentiated and totipotent cells scattered in the extracellular matrix, more recent studies does not seem to support the existence of such undifferentiated cells. Also, very little is known about the genetic program triggered during regeneration within the blastema cells, except some studies reporting the expression of pax6 and otx in the regenerating central nervous system. Within platyhelminthes, most of the cellular and molecular data of the regenerative process comes from planarians, macrostomids are providing also some interesting data. In planarians, wound healing is followed by the local proliferation of totipotent stem cells (known as neoblasts) closed to the wound that originate a regenerative blastema in which the new structures differentiate. Remodelling of the pre-existing tissues is also necessary to achieve normal body proportions of the regenerated animal. Recently, many papers have reported on different genes and signalling pathways that regulate proper regeneration in planarians. However, much more data should be provided from those taxonomic groups that have either poor regenerative capabilities or for which the cellular and molecular basis of their regenerative capacities are currently unknown. Finally, very little is known about the cellular and molecular processes involved in regeneration in molluscs. A recent report on octopus arm regeneration suggests that a mass of mesenchymal undifferentiated cells would accumulate below the wound forming a highly proliferative blastema.

From all these data and comparative analysis in these spiralian phyla the authors draw four main conclusions: 1) the ability to regenerate the whole body seems to be present in only a subset of representatives of each of these groups. From a phylogenetic perspective numerous increases and/or decreases in regeneration ability have occurred across these phyla. This raises that the possibility that regeneration may not be homologous across them needs to be considered; 2) posterior regeneration appears to be more widespread than anterior regeneration; 3) all phyla include a blastema stage, although the origin of the regenerative cells that form it may be different, and 4) in all these phyla the capacity for continuous growth and degrowth is well documented, suggesting a mechanistic relationship or common set of elements and features between these processes and regeneration.

In summary, how the capacity of regeneration has evolved is also a fascinating field of study that requires much more sampling and data collection for the required comparative analyses.

Happy New Year!!!

Dear readers

I just posted an annual report of this blog prepared by WordPress. I am very happy to see how the number of visits to this site has increased compared to 2013. So thank you very much to all of you that regularly or occasionally read my posts. And also, special thanks to those of you (very few yet) that comment on some of the posts. Unfortunately I couldn’t write any new post the last weeks of December as I got a lot of teaching. But I will be back very soon. So keep ready to read more about regeneration



2014 in review

The stats helper monkeys prepared a 2014 annual report for this blog.

Here’s an excerpt:

The concert hall at the Sydney Opera House holds 2,700 people. This blog was viewed about 13,000 times in 2014. If it were a concert at Sydney Opera House, it would take about 5 sold-out performances for that many people to see it.

Click here to see the complete report.

Regeneration is out

Few months ago I  informed you about “Regeneration”, the first scientific journal dedicated exclusively to our field. Now, the first issue is already out online. You can check the first publications at: (

Congratulations to everybody working for the succeed of this journal. I wish we can all collaborate to make it a reference journal

One year of “Regeneration in nature”

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 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”.

Happy New Year 2014!

This is a short post just to wish all of you a happy new year. I hope 2014 will be an exciting year for regeneration and it will bring us tens of papers reporting novel data on how our beloved friends are able to regrow injured or lost organs, structures and body parts. I will stay here blogging about basic research focussed on understanding this fascinating biological process.

Regeneration Journal

This week I am not going to comment on any specific paper on regeneration but rather publicize the launch of a new journal dedicated to this fascinating field of regeneration. The new journal is called Regeneration and will be published by John Wiley & Sons ( The Editor-in-Chief is Susan V. Bryant a prestigious researcher in the field of limb regeneration in amphibians. The associate editors include Kiyokazu Agata, Enrique Amaya, Cheng-Ming Chuong, Ken Muneoka, Ken Poss and Elliot Meyerowitz. Regeneration is an open access journal and will be the first journal to be dedicated exclusively to regeneration and tissue repair in animals and plants. Therefore the regeneration community have now an excellent tool to disseminate our results in a more compact way that should make more visible our advances and research and, at the same time, attract more people to this field. Hopefully this journal will be useful also to establish bridges between naturally occurring regeneration and the need to enhance assisted regeneration. I really hope that we can all contribute to the success of this journal. I will keep you posted when the first issue is available.

Back to blogging

Dear all

I hope you all have had nice holidays. After a long summer break I am ready to continue my blogging activity on animal regeneration. As I have been doing in the last several months I will publish a new post every Thursday, starting this week. I hope you will enjoy them. And please, feel free to comment on any aspect of them in order that we all can promote some helpful and interesting discussions.

Summer break

Just a short note to inform you that I will be taking a summer break in the following weeks. A few months have already passed since I started this blog and I must say that it has been a very gratifying experience. Thank you very much to all of you that regularly follow this blog or occasionally read some of my posts. And also, thank you very much for your comments on the issues discussed. I will be back in September, after attending the 2nd European Meeting on Planarian Biology to be held in Dresden (, with renewed energy to keep posting about this fascinating process of regeneration in nature.

Spinal cord regeneration in vertebrates

Patients of neurodegenerative diseases such as Alzheimer and Parkinson as well as people that suffer spinal cord injuries would surely benefit if we would manage to enhance somehow the very limited regenerative capacities of our central nervous system. But whereas mammals show almost no regeneration potential in their CNS, other vertebrates such as amphibians and zebrafish are capable of regenerating their spinal cord. Also, invertebrates such as planarians can regenerate a complete CNS de novo from any small piece of their bodies. So, how do amphibians and fish do to regenerate their spinal cord? What prevents mammals from doing the same? Because of the great potential benefits of enhancing mammalian CNS regeneration a lot of research is being done in this field; however, the results are not being really very promising yet, at least as fast as demanded by the society.

In a recent review from the laboratory of Karen Echeverri the authors discuss the current state-of-the-art of vertebrate CNS regeneration ( When comparing the regenerative response of mammals to that from amphibians and fish important aspects that need to be considered include the cellular response to injuries and the formation and role of the glial scar. In zebrafish, upon injury, glial cells amplify and migrate to the lesion where they elongate creating a glial bridge that axons use as a scaffold to grow across the lesion. A very interesting observation in zebrafish is that the re-wiring of the regenerated CNS does not need to be one hundred per cent accurate (in terms of re-establishing the original connections) to yield a functional recovery.

Amphibians, both anurans (tailless amphibians) and urodeles (tailed amphibians) regenerate the spinal cord during tail regeneration. In Xenopus it has been described a population of putative neural stem cells positive for Sox-2 that, upon injury, proliferate and migrate forming a substrate for axonal regeneration. In urodeles, also, fibroblasts and glial cells migrate to create a substrate for axonal regeneration. Thus, in all these models once the spinal cord is injured certain cell types are able to create a regeneration-permissive environment.  Another thing that is shared by amphibians and zebrafish refers to the upregulation of signalling pathways such as Wnt, BMP and FGF during spinal cord regeneration.

In contrast, CNS regeneration in mammals is inhibited by both extrinsic and intrinsic factors. One of the most important inhibitors is the glial scar that acts as a physical and chemical barrier to regeneration. In zebrafish and amphibians, however, no inhibitory glial scar is formed. Recently it is emerging the view that in mammals the glial scar although inhibiting axonal regeneration may have an important role as a protective agent during early stages after injury. In this sense it becomes interesting to further analyse whether the inhibitory action of the glial scar on regeneration is an unavoidable trade-off of its beneficial role on stabilizing the injury site preventing further damage. If this is true maybe it means that there is a kind of evolutionary constraint that really works against the possibility of enhancing CNS regeneration in mammals. Another field to develop is the study of the inhibitory action on regeneration by myelin components such us Nogo, myelin-associated protein (MAG) and oligodendrocyte-myelin glycoprotein (OMgp). Different studies have shown contradictory results in terms of enhancing the regenerative capabilities after inhibiting these factors. Therefore more data and comparative analyses are needed from animals that can and cannot regenerate their CNS.

In summary, and as it has been pointed out in previous posts on this blog, it is important not only to understand as deeply as possible how regeneration takes place at both cellular and molecular level, but also to try to determine why the regeneration potential has been lost in certain lineages. In this sense spinal cord regeneration provides with a very attractive model in which direct comparisons between regenerating and non-regenerating models (phylogenetically close, such as amphibians, fish and mammals) can be beneficial for the field as it may help, for example, to determine what really makes that some species are able to create a regeneration-permissive environment whereas others, in which similar cell types and molecular pathways are present and even upregulated after injury, cannot do it.

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