Limb Regeneration Might Have Been The Original State For All Four-Legged Animals

Fossil amphibian Sclerocephalus from the lower Permian of Germany. Hwa Ja Goetz/MfN
Josh Davis 26 Oct 2015, 14:33

Of all living four-legged animals, known as tetrapods, only salamanders have the ability to truly regenerate their limbs. Scientists have long questioned this impressive feat, because all other tetrapods develop their limbs in a strikingly similar way, making salamanders seem like the black sheep. But new research hints at the possibility that rather than being an evolutionary oddity, salamanders are actually the only ones to have retained this ability, which was once common to all tetrapods.

The study, published in Nature, looked back at fossil tetrapods from the early lineages of both amphibians (frogs, salamanders, and caecilians) and amniotes (mammals, birds, and reptiles), from around 300 million years ago. This is roughly 30 million years after the two groups are thought to have split, and so the logic goes that if fossils from both lineages at around this time share characteristics, it’s highly likely that the last common ancestor before the split had these characteristics, too.

When animals re-grow limbs, they sometimes leave tell-tale signs such as fused digits, extra digits, or digits missing altogether. It was these signs that the researchers were looking for in the record from both groups, and this is exactly what the researchers found in the fossils from both lineages, indicating that they could both indeed regenerate body parts. This leaves the intriguing proposition, though, that while salamanders were able to hold onto limb regeneration, most other four-legged animals lost it.  

Drawing of the fossil amphibian Micromelerpeton credneri showing limb regeneration, and how malformations can occur. Kalliopi Monoyios/Science Illustration & Communication      

“At first sight it is astonishing that a character that is so obviously beneficial like the capacity of limb regeneration has been lost in most extant tetrapods (i.e., in all amniotes),” Brown’s Florian Witzmann told IFLScience in an email. “We have no definite explanation for this, although a number of hypotheses exist related to the cost-benefit ratio of regeneration. Regeneration of limbs and other parts of the body is certainly energy expensive, and in some cases, the costs might be greater than any advantages.”

One suggestion is that for animals with a short lifespan that grow and develop quickly, it might be more beneficial to spend energy on creating as many offspring as possible, rather than regenerating limbs, which can take quite a long period of time. However, exactly why frogs lost the ability, but salamanders retained it, is still unknown, but it seems that once the ability was lost, it could not be regained. For amniotes, though, there might be a slightly different explanation for the loss of regeneration.

“There exists a well-founded hypothesis of why amniotes are not capable of limb regeneration (in contrast to salamanders),” says Witzmann. “In short, this hypothesis proposes that the capacity of limb regeneration is correlated with the timing of when the limbs develop in the embryo.” Amniotes form limbs early on during development which might “lock” them in, whereas with amphibians the limbs develop later on and are classed as “self-organizing.” It could be that this later development could be a requirement for regenerative capabilities when in adulthood.

This new finding, that limb regeneration is actually a primitive ability which was once common for all tetrapods, is really quite surprising. It could also hold some important clues for biomedicine and the quest to figure out how limbs regenerate, and whether it could one day be applied to humans. 

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