Why do some animals grow back missing body parts?

Specimens of various flatworm species

Flatworm species, such as those pictured here, vary significantly in their ability to regrow body parts. This could, among other things, have to do with how they reproduce. © Miquel Vila-Farré/ Max Planck Institute for Multidisciplinary Natural Sciences

Unlike humans, some animal species grow back injured or severed body parts. Missing arms, legs or other limbs are simply replaced with new ones. But why don't all animals have this ability to regenerate? A study on flatworms now provides new evidence. Accordingly, worms that reproduce asexually grow limbs. The researchers conclude that the ability to regenerate could have developed in parallel with the reproductive strategy as an evolutionary compromise.

Some species, including some spiders, snails, zebrafish, salamanders and axolotls, can regrow missing or injured body parts or even almost entire bodies. Regeneration works particularly well with some types of flatworms: if you cut them up, a new worm grows from each piece. Other flatworm species, however, cannot replace defective tissues or organs. “This form of regeneration seems to be the exception in the animal world, although it should offer great advantages for survival,” says senior author Jochen Rink from the Max Planck Institute for Multidisciplinary Natural Sciences in Göttingen. Why then do so many animals, including us humans, lack this ability to regenerate?

Previous experiments by his research team had already shed light on how the ability to regenerate is controlled. “When flatworms regenerate, the so-called Wnt signal transmission pathway works like a molecular switch,” explains the cell biologist. If this signaling pathway is “switched on,” the worms grow a tail; if it is “switched off,” a head forms. If the signaling pathway is completely blocked, the overall ability to regenerate improves. Now Rink's team, led by lead author Miquel Vila-Farré, has also investigated in which flatworm species this mechanism is particularly effective and when it developed in the course of evolution. To do this, the researchers examined the extent to which they can regrow their heads in 36 different species of flatworms after they were decapitated. This was made possible by the institute's extensive flatworm collections.

Flatworms in the regeneration test

This showed that the flatworm species can regenerate at different rates. “We found three groups,” describes Vila-Farré. “The first group has poor to no regenerative abilities, the second has limited ability to replace body parts and the third has reliable head regeneration.” The limited regeneration abilities were always based on the Wnt signaling pathway. In a supplementary family tree analysis, the scientists then reconstructed at what point in evolution the different species developed or lost their ability to regenerate their heads. It turned out: “The ability to regrow organs and tissues has developed independently several times in different flatworm species and has also been lost independently in different species over time,” says Vila-Farré, summarizing her observations.

But why hasn't the ability been preserved? As the comparisons showed, the flatworm species also differ in their reproductive strategy: they reproduce either asexually or sexually. The researchers therefore suspected that this could influence the ability to regenerate. To investigate this theory, they specifically tested different strains of the flatworm species “Schmidtea mediterranea” to see whether severed body parts regrow and how active their Wnt signaling pathway is. They discovered that flatworms that reproduce asexually split into two parts, each of which grows into a new worm. “These species need regenerative abilities to reproduce,” concludes Vila-Farré. In contrast, the worm species that only partially regrow missing limbs reproduce almost exclusively sexually. “They lay eggs and do not need to reproduce any body parts to reproduce,” explains Vila-Farré. His team also found corresponding differences at the molecular level: the molecular switch of the Wnt signaling pathway was significantly more active in the strains that reproduce sexually than in strains that reproduce asexually.

Compromise between reproduction and regeneration?

The researchers conclude that the Wnt signaling pathway also plays an important role in the development of the reproductive system. “The gain or loss of regenerative abilities in different flatworm species could be due to interactions between the Wnt signaling pathway and the reproductive system,” explains Rink. The researchers suspect that Wnt signals promote the formation of testes and egg yolks, but at the expense of the ability to regenerate, as this requires inhibition of Wnt signals.

Accordingly, switching the Wnt signaling pathway on and off could be an evolutionary compromise: either effective sexual reproduction and poor regeneration, or vice versa. "Our assumption is that the regenerative ability in flatworms did not evolve to 'repair' wounds, but rather to asexual reproduction through division," says Rink. This could explain why species with and without the ability to regenerate have emerged in nature. Further studies must now show whether this hypothesis is correct and whether there are other animal groups in which this connection comes into play. Further research should also be carried out into whether environmental influences have influenced the evolutionary development of the ability to regenerate.

Source: Vila-Farré (Max Planck Institute for Multidisciplinary Natural Sciences) et al., Nature Ecology and Evolution, doi: 10.1038/s41559-023-02221-7

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