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Home » Cnidarians » Epimorphic regeneration in Nematostella and the use of the terms “epimorphosis” and “morphallaxis” in regeneration

Epimorphic regeneration in Nematostella and the use of the terms “epimorphosis” and “morphallaxis” in regeneration

In a recent paper Passamaneck and Martindale show that cell proliferation is necessary for  regeneration in Nematostella ( By blocking cell proliferation the authors are able to block also regeneration, suggesting that contrary to what it has been described in Hydra, Nematostella does not appear to have any other compensatory mechanism to allow regeneration in a context of no proliferation. This finding is relevant because it shows how different cnidarian species may use very different modes of regeneration based on the classically used terms of “epimorphosis” and “morphallaxis”.

Originally, in 1901 Thomas H. Morgan wrote that “… there are known two general ways in which regeneration may take place, although the two processes are not sharply separated, and may even appear combined in the same form. In order to distinguish broadly these two modes I propose to call those cases of regeneration in which proliferation of material precedes the development of the new part, epimorphosis. The other mode, in which a part is transformed directly into a new organism, or part of an organism without proliferation at the cut surfaces, morphallaxis”. Based on this definition it appears that when regeneration requires proliferation then it would be epimorhic regeneration, whereas regeneration in the absence of proliferation would be morphallactic. A more updated use of the term “epimorphic” includes also the definition by Richard J. Goss (The natural history (and mistery) of regeneration, 1991. In A History of Regeneration Research. Milestones in the evolution of a science, Ed. C.E. Dinsmore) and that states that “Epimorphic regeneration refers to the regrowth of amputated structures from an anatomically complex stump”, and that “The first event in epimorphic regeneration is the development of a blastema, or regeneration bud, derived from dedifferentiated cells, out of which the new structure will take shape”. So, the consensus is that epimorphic regeneration requires proliferation and the formation of a blastema. But not all blastemas are derived from dedifferentiated cells as stated in Goss definition. That is valid, for instance, for amphibian limb regeneration. But in planarians, regeneration occurs mainly by cell proliferation and the formation of a blastema that is derived from adult pluripotent stem cells and not after dedifferentiation.

But whereas the idea of epimorphic regeneration is quite well-established it cannot be said probably the same for the term of “morphallaxis”. Thus, Hydra has been usually used as an example of “morphallactic” regeneration because it has been know for many years that they can regenerate in the absence of proliferation or without a significant contribution of this proliferation. However, in 2009 the laboratory of Brigitte Galliot showed that in Hydra, and after midgastric bisection, head regeneration depends on an initial apoptotic response below the wound that triggers a proliferative zone with “blastema-like” features that significantly contributes to oral regeneration ( So, in that particular context regeneration seems to be “epimorphic”. As Morgan already said in his definitions, both processes, epimorphosis and morphallaxis, are not mutually exclusive. A good example of that are freshwater planarians that have been considered to follow a mixed epimorphic/morphallactic mode of regeneration. The basis of that is that in addition to the fundamental role of pluripotent stem cells in giving rise a regenerative blastema where the missing structures are formed, there is also a remodeling of the pre-existing tissues far away from the wound that help to attain the proper body proportions during regeneration. This remodeling, considered as morphallactic, is more evident in for example in head and tail pieces regenerating a new whole planarian. Thus, if you start with a big head piece containing a big brain it regenerates not only the whole body posterior to this head (through proliferation, blastema formation and growth of the regenerated part) but at the same time the original head with its brain go through an extensive remodeling so they decrease significantly in size in order to form a smaller planarian with perfect body (head/trunk/tail) proportions. So, following Morgan’s definition of morphallaxis at the beginning of this post literally, this remodeling would not require proliferation. However, a paper from the laboratory of Alejandro Sánchez-Alvarado on the temporal and spatial dynamics of Wnt genes expression during planarian regeneration shows that “… although pre-existing cells can assess their new A/P position in the absence of stem cells, anatomical tissue remodeling in planarians depends on the presence of stem cells” ( Therefore, this data would point out that “morphallaxis” could depend somehow also on proliferation.

To solve this apparent conflict one possibility could be to restrict the term of “morphallaxis” to the first definition given by the same Morgan in 1898 in which he wrote: “Thus, the relative proportions of the planarian are attained by a remodeling of the old tissue. I would suggest that this process of transformation be called a process of morpholaxis”. Then, “morphallaxis” can be clearly associated to “remodeling of the pre-existing tissues” and this would be “proliferation dependent” or “proliferation-independent” depending on the organism (planarian/Hydra) or the specific context of regeneration.



  1. Jaume Baguñà says:

    This is another of my favourite items regarding regeneration and T.H. Morgan: epimorphosis vs morphallaxis. Let me state from the very beginning that I consider them useless and confusing concepts and, therefore, dispensable.

    A general comment on Morgan and cells, and two specific ones on morphallaxis and epimorphosis. When TH Morgan proposed these concepts (1901) he did it without paying much attention (actually he could not do otherwise) to its cellular nature. At that time, planarian parenchyma was considered a syncitium within which neoblasts wandered (wandering cells; stem cells; etc,..). And despite Gelei (1912) using osmium tetroxide as fixative, and Prenant (1922) making the first dissociation/maceration experiments, showed parenchyma to be cellular, nobody payed attention to them until EM did the job (Pedersen, 1959) and proved them right. Therefore, Morgan only had a very slight idea, in cellular terms, of what morphallaxis, and even epimorphosis, implied as applied to regeneration, namely in planarians.

    Now let’s talk on morphallaxis. What was in Morgan’s head? What did he mean by the remodelling of the old tissue without cell proliferation in planarians? Transdifferentiation of cells? Cell death and ‘reorganization’ of remaining cells? Cell death and differentiation of some cells from neoblasts? Moreover, he could not state that proliferation had no role in it, because there are lots of proliferating cells in remodelling planarians. To be brief: he had a very coarse macrosopic idea because he did not have the tools to go further. Now in Nematostella, belonging to the cannonical morphallactic group, the cnidarians, Passamaneck and Martindale (2012) report that cell proliferation is necessary. Even in Hydra regeneration, Holstein, Hobmayer and David (Dev Biol. 148:602-611, 2001); and Holstein, Hobmayer and Technau (Dev Dyn; 226:257-267, 2003) had already questioned its morphallactic nature showing that 30hr after cutting there is a burst of S-phase cells at the regenerating head tip, as it also happens during bud development. Moreover, hydroxyurea and aphidicoline treatments inhibited cell proliferation and lead to incomplete regeneration. In other words, first in Hydra and now in Nematostella, two classical morphallactic models, proliferation is necessary. Therefore, neither regenerating hydras nor remodelling planarians fit Morgan’s concept of morphallaxis. In my view then, ‘proliferation-dependent morphallaxis’ or proliferation-independent morphallaxis’ as suggested as a compromise by Francesc Cebrià is of little help as both systems require proliferation. The question now is: is there a pure (remodelling without cell proliferation) morphallactic system?

    Let’s turn our attention to epimorphosis. Morgan stated ” I propose to call those cases of regeneration in which proliferation of material precedes the development of the new part, epimorphosis”, and 90 years later (1991) RJ Goss wrotte “Epimorphic regeneration refers to the regrowth of amputated structures from an anatomically complex stump” and “the first event in epimorphic regeneration is the development of a blastema, or regeneration bud, derived from dedifferentiated cells, out of which the new structure will take shape”. F. Cebrià is quite right critizising Goss’ ‘amphibiancentric’ view of regeneration with dedifferentiation as the sole source of blastema cells. Even for amphibians, we know today this is not correct. But here again, Nature’s variability is bewildering. Focusing on plathelminthes (flatworms and the like) some of them, like classical planarians (Tricladida) form a blastema (from undifferentiated cells or neoblasts) although blastema cells do not proliferate (at least in anterior blastemas; in posterior blastemas they do). Others (Catenulida, microstomids) do not form a blastema but undifferentiated cells (neoblasts) proliferate and new organs form, within the old part after wound healing, by cell migration, aggregation, and external (outer) cell acretion. From the outside, some could call it ‘morphallaxis’. Although there are other examples, better to stop here.

    In summary. Epimorphosis and morphallaxis, taken as pure concepts do not exist and are rather confusing. Suggesting, as Morgan first and others later did, that “the two processes are not sharply separated, and may even appear combined in the same form” does not help much, because adds more confusion to a rather confused field. I therefore propose to leave out them.

    At least for me, Morphallaxis and Epimorphosis are dead. Long life to Regeneration!!


    • It is obvious that what we currently know on how regeneration works at the cellular level is very different from what Morgan knew when he proposed the terms “epimorphosis” and “morphallaxis”. And in fact, over the years these terms have been modulated and discussed under the light of our increasing knowledge of regeneration not only in classic models but in new models of regeneration. So I can agree with the view of Jaume Baguñà that the concepts “epimorphosis” and “morphollaxis” appear outdated in terms of Morgan’s stricted definition. However, it is also true that Morgan realized of the two general main modes of regeneration that certainly most animals broadly follow (or processes through which regenerative models go). He saw that, on one side, regeneration depends clearly on cell proliferation to provide cells to build up the missing structures and that, on the other side, the pre-existing tissues far away from the amputation plane can go through an extensive remodeling that is also pivotal for proper regeneration. These two processes can be combined in the same animal, as for instance in freshwater planarians.

      Consequently, as these features are quite general among the regeneration models we need, in my opinion, terms to refer to them. What I wanted to mean in my original post is that probably the term “epimorphosis” is still useful to refer the mode of regeneration in which the new structures are built up within a blastema distal to the amputation plane and requiring proliferation to provide the required cellular source for this regeneration. And that, independently on whether proliferative cells are pluripotent stem cells or dedifferentiated cells and whether cell proliferation occurs within or outside the blastema. On the other hand, for the term “morphallaxis” what I was meaning is that defining it basically in terms of lack of proliferation is what is rather debatable to me based on our current knowledge. Here, I agree with Jaume Baguñà’s question on whether pure, strict morphallaxis really occurs naturally. And in fact, what I was proposing was to go back to the idea of using the term “remodelling” instead, independently on whether that remodelling takes place naturally in the absence of proliferation or it also requires proliferation in regions close or far away from the remodellating tissues.

      To summarize, I agree that many times the terms we use need to get adapted and redefined based on our current knowledge but that does not necessarily mean to have to abandon them completely. Let’s make the effort to update them in an open debate and of course…Long Life to Regeneration!


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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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