One of the most fascinating things about some amphibians, notably certain salamander species, is their ability to fully regrow lost limbs throughout their entire lifespan. Given the fact that frogs are also amphibians, it is easy to think that they can possibly regrow lost or broken limbs as well. But frogs are not like salamanders.
Frog tadpoles can generally regrow lost limbs, however frogs lose this ability at the adult stage. African Clawed Frogs are an exception as this species is somewhat able to regenerate lost limbs in such a way that it resembles a claw or a spike of cartilage.
One of the most interesting amphibians on earth is the Axolotl, a type of salamander. Axolotls are capable of fully regenerating lost limbs. The process may take a long time, but the regenerated limb will eventually resemble the lost one and be fully functional. But this ability is fairly exceptional in the amphibian wold as a percentage, since frogs make up the vast majority of amphibians.
Frogs can generally regrow or regenerate tails (Chen, 2018), legs, and feet at the tadpole stage. However, when tadpoles fully metamorphose into frogs, they lose the ability to regrow and generate their limbs. This is the general rule among most frog species. But it is interesting to note that there is one frog species that has a unique ability that most frogs do not.
African Clawed Frogs Can “Regrow” Limbs
However, among over 7,400 frog species, there is one type of frog that is somewhat capable of regrowing its limbs to a certain extent: the African Clawed Frog (Xenopus laevis). African Clawed Frogs do not lose the ability to regrow limbs once transformed from tadpole to adult. However, regenerated limbs only resemble a claw or a spike of cartilage and are not a fully functional.
When the leg of an adult African Clawed Frog is amputated due to an accident or an encounter with a predator, the amputated area will undergo a regeneration process that allows a pointy spike or claw-like piece of cartilage to grow. Therefore, African Clawed Frogs cannot not regrow a fully functional limb like Axolotls. However, scientists were able to find a way to try to trigger further regeneration in the African Clawed Frog using progesterone
Herrera-Rincon et al. (2018) applied progesterone an amputated hind-leg of the African Clawed Frog and found it accelerated the regrowth of a paddle-shaped limb that seemed to suggest that it was closer to regrowing into an actual leg. Meanwhile, the control group that did not receive the hormone treatment continued to grow the spike-like cartilage that African Clawed Frogs are known for.
This team of scientists continued to observe the frogs that received the hormone treatment but soon observed that the limbs stopped growing after six months. At this point, the regenerated appendage started to show fingers and toes that were yet to fully develop. Meanwhile, the regenerated limb also exhibited stronger bones and organized nerves and blood vessels that allowed the frog to display activity levels that are similar to counterparts that never lost their legs.
The research suggested that it was possible for these frogs to regrow their limbs with the right kind of hormone treatment. However, because of the fact that African Clawed Frogs do not receive progesterone treatment in the wild, it would be impossible for them to fully regrow their limbs in the same way as Axolotls.
Why Frogs Cannot Fully Regrow Limbs
A different group of scientists (Lin et al. 2021) studied the reasons why the African Clawed Frog, or any other frog for that matter, cannot fully regrow limbs in the same way as Axolotls.
When an Axolotl loses a limb, different types of cells migrate to that are to form what is called a blastema, which is a lump of dedifferentiated cells that serve the purpose of rebuilding the lost limb. In most vertebrates, what happens is that the cells would merely build a scar in an area that got hurt but will not proceed to rebuild a limb that was lost.
African Clawed Frogs do not generate the same regenerative cells as Axolotls. Scientists remarked that the reason could be related to the nature of the frog’s cell composition, or even the frog’s own immune system.
Chen et al. (2021) tried injecting the blastema cells to an African Clawed Frog tadpole, which is capable of fully regenerating its limbs. However, the cells remained unresponsive and could not help the tadpole regenerate its limbs (CTNF), possibly due to the frog’s genes being over or under-expressed after it went through the process of metamorphosis.
More About Frogs And Limb Regrowth
Scientists are looking at frogs and axolotls not only to better understand how they regenerate limbs, but also to understand why humans cannot, and how we can integrate this incredible capacity into our own medicine.
Learn more about frogs and limb regrowth on our blog:
Herrera-Rincon, Celia; Golding, Annie S.; Moran, Kristine M.; Carabello, Hayley; Kaplan, David L.; Levin, Michael; Brief Local Application of Progesterone via a Wearable Bioreactor Induces Long-Term Regenerative Response in Adult Xenopus Hindlimb, Volume 25, Issue 6, P1593-1609.E7, November 2018, DOI: https://doi.org/10.1016/j.celrep.2018.10.010
Lin, Tzi-Yang; Gerber, Tobias; Taniguchi-Sugiura, Yuka; Shibata, Eri; Treutlein, Barbara;
Tanaka, Elly M.; Fibroblast dedifferentiation as a determinant of successful regeneration Volume 56, Issue 10, P1541-1551.E6, May 2021 DOI: https://doi.org/10.1016/j.devcel.2021.04.016
Chen Y, Love NR, Amaya E. Tadpole tail regeneration in Xenopus. Biochem Soc Trans. 2014 Jun;42(3):617-23. doi: 10.1042/BST20140061. PMID: 24849228.