Salamander ancestors could regenerate limbs

Losing a limb or a tail isn’t too worrisome for salamanders. They can regenerate lost appendages. And so could a number of their ancient relatives, a new study finds.

Amphibian fossils from 290 million years ago show signs of the animals regrowing limbs, researchers report online October 26 in Nature. The findings suggest that some salamander ancestors had the ability to regenerate body parts nearly 80 million years before the first salamander existed.

The results “show that salamander-like regeneration is not something that is salamander specific, but was instead widespread in the evolutionary past,” says study coauthor Nadia Fröbisch, a paleontologist at the Museum of Natural History in Berlin.

Sea stars, frogs and even humans (in the liver) have some degree of regenerative ability at various life stages. But salamanders are one of the few living four-legged animals that can fully regenerate entire limb bones, nerves and muscles throughout their lifetimes. In other animals that can regenerate arms and legs, bones in the hands or feet that are on the outside edge tend to form first. In salamanders, though, it’s the bones on the inside edge; the thumb before the pinky.

Fossils of various ancient amphibians show a similar regenerative pattern, Fröbisch and colleagues report. The new study builds on some of Fröbisch’s previous work  with a single species of ancient amphibian that showed the kind of limb abnormalities also seen in modern salamanders that are growing a new limb. 

“If we had only one animal showing particular traits related to skeletal growth, we could not say much about common patterns or the mechanisms that produce those patterns,” says Jennifer Olori, a study coauthor and evolutionary biologist at State University of New York at Oswego. “When we combine information from across these groups, using the new information from additional fossils, it allows us to predict which traits may have been inherited from an older ancestor.”

A second study shows a molecular basis for the odd way that salamanders regenerate limbs. During early regenerative growth, genes called orphan genes are active, report Anoop Kumar of University College London and colleagues October 26 in Nature Communications. Some of these genes are also crucial in digit formation in amniotes, a group including reptiles, mammals and birds but not amphibians.

A few of those animals — like lizards that can regrow their tail — have some regenerative powers. But for now, salamanders and their ancient amphibian relatives remain the kings of vertebrate regeneration.

“The idea that regenerative capacity was much more widespread in nonamniote species is a significant finding,” says Hillary Maddin, a paleontologist at Carleton University in Ottawa who was not involved with either study.

“It suggests that we, and maybe amniotes in general, are much more alone in the lack of an ability to regenerate limbs,” she says. “It becomes tempting to think that amniotes are hiding a latent capacity to perform complex regeneration, and the correlation with a potential molecular mechanism, orphan genes, points to a good place to start.”