regeneration in nature

Home » Acoels » Polarity re-establishment during regeneration in the acoel Hofstenia miamia

Polarity re-establishment during regeneration in the acoel Hofstenia miamia

Regeneration is quite widespread across phylogeny; however, not many species are capable of regenerating a whole animal from a tiny piece of their bodies. And, even in those species, we miss in many of them a deep knowledge of the gene and molecular pathways that control the different events that lead to a successful regeneration. Some positive exceptions are found within Platyhelminthes and Hydra. To understand regeneration from an evolutionary perspective it is necessary to characterize how regeneration occurs at the cellular, molecular and gene levels in as many species as possible from different phyla.

Acoel worms are simple animals belonging to the phylum Acoelomorpha. These animals were classically included within the Platyhelminthes. However, in 1999 some phylogenetic analyses placed them outside the Platyhelminthes. Acoels together with nematodermatids form the phylum Acoelomorpha and for many years have been considered as basal bilaterians. In a new twist, more recent analyses have grouped acoels with Xenoturbella and associated them to Deuterostomates. Therefore, the exact phylogenetic position of acoels is still under discussion. Acoels are capable of whole-body regeneration as previously described for several species (for instance, Isodiametra pulchra) in which it would depend on the presence of adult stem cells.

Now, the laboratory of Peter Reddien has presented a novel model to study whole-body regeneration: the acoel Hofstenia miamia ( These animals are capable of regenerating a new head and tail after transverse amputation. In addition to describing how regeneration takes place in these animals the authors report transcriptomic data corresponding to 16,986 nonredundant gene contigs, which will prove to be an excellent tool for future molecular and comparative analyses. Here, the authors mainly compare regeneration in Hofstenia with what is known in freshwater planarians (Platyhelminhtes). Similarly to what has been described in other acoels regeneration in Hofstenia implies the formation of a regenerative blastema, which appears to be dependent on proliferative stem cells that express the piwi gene marker. Similarly to freshwater planarians most of the mitotic cells concentrate outside the blastema at its base, whereas the blastema would consist of post-mitotic progeny. Also, as in planarians, regeneration appears to proceed through a combination of an epimorphic blastema-dependent stage as well as the remodelling of pre-existing tissues.

The authors also provide evidence that RNAi is efficient in these animals (as it has been proved in other acoels); importantly, in this study, they systematically characterize the expression patterns and silence a large number of genes of the Wnt/b-catenin and BMP signalling pathways to analyse their role during axial re-specification. Remarkably, they found that silencing of b-catenin transform tails into heads whereas the ectopic activation of b-catenin leads to the opposite phenotype: heads are transformed into tails. Therefore, the Wnt/b-catenin pathway plays a conserved role in the re-establishment of AP polarity during regeneration, as it happens in planarians and Hydra. Similarly, their functional analyses with several elements of the BMP pathway revealed its role in DV axial polarity. Thus, the silencing of BMP lead to the ventralization of the dorsal side of these animals.

Finally, the authors carried out some phylogenetic analyses using large-scale transcriptomic data from Hofstenia miamia that, compared to other species, is a slow-rate evolving acoel. From the data obtained the authors support the view that acoels would occupy a basal position among bilaterians, although this should be further corroborated by the analyses of further genomic data from several other species of acoels.

What is important from an evolutionary perspective is the remarkable similarities between how acoels and planarians (separated by more than 500 million years) carry out whole-body regeneration. As the Wnt/b-catenin and BMP pathways are also important for the establishment of axial polarity during the embryonic development of most animals, the fact that they are also required during regeneration in acoels and planarians could be interpreted in two different ways: 1) the last common ancestor of acoels and planarians was able to regenerate using also these pathways, or 2) these pathways were independently co-opted for regeneration in both groups because of their pivotal role in polarity during embryogenesis. On the other side, if the last common ancestor of bilaterians was capable of regenerating it should be possible then to find additional similarities between whole-body regeneration in acoels and planarians, for example. And, certainly, several similarities exist: they have piwi+ proliferative cells with similar distribution, regeneration depends upon those piwi+ cells, regeneration occurs through blastema formation and remodelling of the pre-existing tissues and important patterning genes are expressed in subepidermal domains in the adults of both groups.

In summary, the authors provide here with a new model and tools for further comparative analyses between whole-body regeneration in different species. Those analyses are necessary for a better understanding of regeneration throughout evolution. But we have to keep in mind that as important as to finding similarities is also to uncover differences and analyse them. For example, in Hofstenia the silencing of a gene called notum transforms a head into a tail, as it happens in planarians. However, whereas in planarians notum is expressed in very few cells at the most anterior tip of the head, in Hofstenia this gene is largely expressed throughout the body but completely excluded from the head. Also, in Hofstenia the silencing of admp significantly ventralizes the dorsal side of their body. In planarians, the silencing of admp by itself does not yield an obvious ventralizing phenotype. But, admp silencing enhances the ventralization that occurs in bmp RNAi animals. Therefore, although notum and admp are necessary for the re-establishment of AP and DV polarity, respectively, in both Hofstenia and planarians, the differences described above could be suggesting slight divergences in the fine molecular mechanisms and relationships through which these elements carry out their functions.



  1. Jaume Baguñà says:

    This is an extremely nice and well produced paper for which I deeply congratulate Peter Reddien and his group. From now on I believe Hofstenia will be the acoel model system as regards embryonic development and regeneration. They will also be instrumental, together with other short branched acoelomorfs, to sort out where acoels (+nemertodermatids) are basal bilaterians (an idea advanced by Ruiz-Trillo et al in Science 1999 from our lab in Barcelona), or derived, though rather basal, deuterostomates (Philippe et al, Nature 2011). Although Reddien et al did a lot to sort it out leaning to for basal bilaterians, more data is needed, namely from short-branched species and from whole genome studies of several species now close (I hope) to be finished.

    The parallelisms between the AP and DV signalling systems between Hofstenia and planarians were to be expected, but it is nice somebody did it. And as regards the similarities between the neoblast system between acoels and planarians it is certainly stricking. I have some ideas on that but from the time being I keep them to myself.


    • One aspect for further discussion, at least for me, related to the function of the BMP pathway in the specification of the DV axis, is that in Protostomes BMP specifies the dorsal side whereas in Deuterostomes it specifies the ventral side. In the case of Hofstenia BMP specifies the dorsal side, as in planarians and, consequently, this would not agree with acoels being close to Deuterostomes, isn’t it? Unless they would represent some intermediate phyla in between this two big groups of bilateral animals.


  2. Naraoia says:

    What sounds most interesting to me from this is the relationship between blastema and proliferation zone. I thought having a proliferation zone just outside the blastema was a distinctly planarian phenomenon (or at least I can’t think of any other examples off the top of my head), but I also think we can be reasonably sure that whatever acoels are, they aren’t flatworms. Intriguing. I’m definitely gonna have to peruse this paper.


    • Yes, you are right although there are some other flatworms, such as Macrostomum, in which proliferation takes place within the blastema. So, even among flatworms there are differences in terms of the distribution of mitotic cells in relation to the blastema. Even though the exact position of acoels is not clear yet, it seems that they could share some of the features observed in different species of Platyhelminthes. And yes, it terms of mitoses outside the blastema this particular species of acoels would resemble the planarian models most used currently.


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Francesc Cebrià

Francesc Cebrià

Francesc Cebrià

I am a Biologist and Professor at the University of Barcelona. I do my research on a fascinating animal: freshwater planarians. You can cut them in as many pieces as you want and each piece will regenerate a complete new flatworm in very few days. In this blog I will keep you updated on the latest news on the field of animal regeneration. You will be able to follow the latest research on how planarians, axolotls, newts, cnidarians and other animals are able to regenerate parts of their bodies

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