regeneration in nature

Home » Planaria » Follistatin promotes planarian regeneration in tissue absence

Follistatin promotes planarian regeneration in tissue absence

A regenerative response can be triggered after several kinds of wounds. In some cases injuries result in loss of tissues or structures whereas in others not. As the regenerative responses that need to be activated in these two situations are expected to be quite different a question to answer is how is this controlled. That is, how the body senses how much it has lost and needs to be rebuilt? Which specific molecular mechanisms are activated to regenerate in tissue absence?

A recent paper from the laboratory of Peter Reddien tackles these questions in freshwater planarians (http://www.ncbi.nlm.nih.gov/pubmed/24040508). Planarians are amazing animals as they can efficiently regenerate after any kind of injury. In the last years it has been shown how upon amputation planarians respond in a quite stereotypical pattern that distinguishes a response driven by small wounds without almost no loss of tissue from that triggered by the loss of large amount of tissue, as it can be for example, head amputation. Thus, upon amputation there is a first general mitotic peak at 6 hours throughout the regenerating fragment that is also observed after any small injury such as a puncture or incision. Then, there is a second mitotic peak at 48 hours just at the wound region adjacent to the blastema. This peak is specific after injuries that result in tissue loss. Similarly, amputation results in a first apoptotic peak at 4 hours mainly concentrated around the wound that, again, is a general response to any kind of wounding. Then, there is a second apoptotic peak at 72 hours more uniformly distributed throughout the regenerating fragment and that is specific for injuries with tissue loss. Finally, the laboratory of Peter Reddien has also identified in the past a collection of genes that are rapidly induced after wounding and whose expression persists in those cases in which regeneration occurs in tissue absence.

In this paper the authors characterize the function of a follistatin homologue in planarians. Follistatins are well known inhibitors of the TGF-beta signalling pathway. Upon silencing follistatin (fst) by RNAi, no defects were observed in intact planarians suggesting that this gene was not required for homeostatic cell turnover. However, treated animals were incapable of regenerating. At the cellular and gene expression level the authors show how after fst silencing and amputation the 1st mitotic peak normally occurred at 6 hours but then the 2nd peak (specific for regeneration in tissue absence) did not take place. Also, the first apoptotic peak was normal in those treated animal whereas the second peak (again the one specific for regeneration in tissue absence) was inhibited. Finally, the authors show how the expression of some of the genes that are wound-induced is not maintained over time as it normally happens in control animals. Upon amputation planarians does not only produce a blastema in which the missing structures will regenerate but the pre-existing tissues are remodelled in order to accommodate the novel proper body proportions. This remodelling is also inhibited after fst silencing. Overall, these results suggest that fst is required to activate a proper regeneration program in the absence of tissue. This is further supported by the fact that there is strong correlation between the kind of injury produced and the level and persistence of fst upregulation. Injuries such as incisions induced fst expression but this did not persist after 48 hours; however, after the excision of lateral tissue wedges, fst expression persisted. Also, a greater fst expression was seen when larger amounts of tissue were missed.

As follistatin is a conserved inhibitor of the TGF-beta superfamily the authors looked for putative TGF-beta ligands that could be regulated by fst. The rationale was to do double silencing of fst and several TGF-beta ligands and see whether any of those double knockdowns was able to suppress the fst RNAi phenotype. The authors found that the co-silencing of fst with planarian either activin-1 (act-1) or activin-2 (act-2) suppressed the fst phenotype; that is, those animals regenerated normally. These results suggest that fst would promote a regenerative response in the context of tissue absence by inhibiting the action of act-1 and act-2. Therefore, it seems that activins would normally inhibit the triggering of a major regenerative response after small injuries that does not imply tissue loss.

In a previous paper from the laboratory of Phil Newmark (commented in this blog on January 24th 2013) the authors had also characterized fst as an essential factor for regeneration and reported that fst would inhibit activin signalling. In that study the authors focussed on a possible role of fst together with notum in defining an organizing center during anterior regeneration. Now, this new paper confirms some of those previous results on fst and activin signalling but expands fst function to a more general role in activating a regenerative program in tissue absence regardless of the polarity of the regenerating fragment.

In summary, this paper describes a pathway that seems to work specifically in activating regeneration in tissue absence and opens the door to further investigate the role of activin (and other TGF-beta ligands) signalling in different models and injury repairing/regenerating contexts.

Advertisements

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out /  Change )

Google+ photo

You are commenting using your Google+ account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

w

Connecting to %s

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

Personal Links

View Full Profile →

%d bloggers like this: