How an axolotl regrows a limb, and what scientists want to learn

Scientists have known for more than 250 years that salamanders can regrow lost limbs. A 2017 review in Trends in Genetics traces the idea back to a paper from 1769, and today the animal doing most of the work in laboratories is the axolotl (Ambystoma mexicanum), a Mexican salamander with feathery gills and a wide mouth that looks like a permanent smile.

The trick is stranger than it sounds. When an axolotl loses a limb, the wound does not scar over. It closes, sends signals and rebuilds, and a 2015 review in Regeneration calls the result complete and faithful: the right bones, muscles and skin come back in the right places. A 2017 review adds that the limb regrows to the correct size whatever the age or size of the animal, and that an animal can be challenged to do it at any point in its life.

This article follows a regrowing limb from the first hours to the finished product, looks at what scientists hope to learn, and says where the story has limits. It ends on a sad twist: the axolotl is easy to find in laboratories and very hard to find in the wild. Axolotls are also kept in captivity outside labs, but this is not a care guide.

Meet the axolotl

The axolotl lives, or used to live, in the Valley of Mexico. The Animal Diversity Web, a University of Michigan database, says the species was native to Lakes Chalco and Xochimilco, that only Xochimilco remains, and that Lake Chalco has been drained. Wild animals are dark and mottled brownish-green. They are carnivores that eat mollusks, fish, arthropods and even other axolotls.

Adults keep feathery external gills and a finned tail, which are larval traits. Biologists call this paedomorphosis, meaning staying young in body form. The Animal Diversity Web says thyroid hormone injections can push an axolotl to metamorphose, but wild ones rarely, if ever, do it. We keep that story short here. The mudpuppy article covers the staying-young angle in full.

The first days: a wound, nerves and a bud of cells

McCusker, Bryant and Gardiner describe the opening moves in some detail. Skin cells cover the wound within hours. That sheet of skin, called the wound epidermis, is reached by nerve fibers within days and turns into a structure named the apical epithelial cap. The cap acts as a signal center: it pushes cells in the stump to dedifferentiate, which means a specialized cell is reprogrammed toward a more embryonic-like state so it can become other things again.

Connective tissue cells called fibroblasts then migrate to the center of the wound under signals from the nerves and the cap, and they re-enter the cell cycle, the cell’s growth-and-division routine. Together these cells form the blastema, which the review defines as a population of regeneration-competent progenitor cells. Progenitor cells are cells that can still turn into several kinds of tissue.

Nerves are not optional. The review says the nerve signal has to reach a threshold. In an experiment with a wound that had no nerve diverted into it, the wound healed but no blastema formed. Limbs that lose their nerve supply form dense scar-like tissue and do not regenerate.

No scar, and a few cells that hold the blueprint

Axolotl wounds start out looking familiar. Fibrosis, the build-up of tough connective tissue, appears for a while and is then remodeled. The review says healing eventually leads to normal skin structure rather than a scar.

Then comes the question of what to rebuild. Not every cell in the blastema knows where it is. Connective tissue cells from the deep skin (dermis) and from around the skeleton keep positional memory, a built-in location tag, and they establish the pattern. Muscle cells, Schwann cells (which wrap nerve fibers) and skin-surface cells lack the tag and follow the pattern set by others. The review reports that almost half of the blastema comes from dermal cells, even though they make up less than 20% of an uninjured limb, and that the contributing cells come from tissue within about 1 millimeter of the cut. Picture a building site where a few foremen carry the blueprints and everyone else follows instructions. That is our analogy, not a claim from the paper.

Beyond limbs, and where regrowth stops

Limbs get the headlines, but the 2015 review says many other parts of an axolotl can regenerate faithfully, including parts of the eye, brain and internal organs. A 2019 review in EvoDevo lists limbs, digits, jaw, tail, heart, gills and liver as structures axolotls readily regrow in experiments.

The same 2019 review draws limits. Axolotls that have gone through metamorphosis keep the ability to regenerate skin and limbs, but at a significantly reduced rate, and they more often regrow limbs that are patterned wrongly. Staying young seems to help. The review also cites a 1976 study in newts, a different salamander group, where limbs failed to regenerate or regrew with defects after as few as five amputations. That is a newt result, and none of our sources gives a matching number for axolotls.

A lizard makes a useful contrast. The five-lined skink drops its tail on purpose and grows a replacement, but the 2015 review notes that in some other animals the regrown structure is not the same as the original.

What scientists study, and why people do not regrow limbs

In 2018 a team from Vienna and Dresden published the axolotl genome in Nature. The news release from the institutes says it has about 32 billion base pairs, the letters of DNA, which is more than ten times the human genome, and it was described as the largest genome sequenced at that time. Co-first author Sergej Nowoshilow said the genome gives researchers a map for investigating how complicated structures such as legs can be regrown. The team also wants to know why regeneration is so limited in most other species.

Plenty is still unknown. The 2017 Trends in Genetics review reports that in one study about 40% of the genes enriched in the blastema had no significant match to known sequences. It also notes an RNA-sequencing study that found an “oncogene burst”: genes with cancer-promoting activity in other organisms are switched on in the regrowing limb. Axolotls can be bred year-round in the lab with relative ease, and genome-editing tools now exist for them.

Why does this matter for people? The 2017 review points out that salamander limbs are anatomically similar to human limbs. The 2019 review says that in mammals, regrowth that rebuilds the lost structure appears limited to the tip of the digit, and that mammals do not ordinarily respond to amputation by growing a blastema. It also reports that salamanders show a reduced inflammatory response after amputation. One hypothesis is that mammals carry roadblocks such as the p16/ARF gene region. In a cited experiment, removing Rb and p16/ARF activity let differentiated mammalian muscle cells re-enter the cell cycle. That is a hypothesis, not a treatment, and none of the sources we read describes a medical use.

Common myths and mix-ups about axolotl regrowth

Myth: an axolotl regrows anything, anytime. Regrowth needs nerves, and animals that have gone through metamorphosis regrow more slowly and less accurately. The newt study above shows that repeated cuts can cause trouble in at least one salamander group.

Mix-up: a regrown limb is just a bigger scar. The opposite is true. With working nerves, the review describes normal skin structure returning, and scar-like tissue appears when the nerves are cut.

Mix-up: lots of axolotls in labs means lots in the wild. The Animal Diversity Web says axolotls are almost extinct in their native habitat, and the lab animals are not living in the lake.

Mix-up: every animal that regrows a part does it the same way. Lizard tails and axolotl limbs are different outcomes, and the review treats them that way.

Conservation status

The axolotl is listed as Critically Endangered on the IUCN Red List of Threatened Species. That is the category as distributed by GBIF, the Global Biodiversity Information Facility, and we checked it on November 9, 2026. Critically Endangered means the species faces an extremely high risk of extinction in the wild, the highest threat category for a species still living there.

The pressures are documented. Conservation International names habitat degradation, pesticide use in farming, and invasive carp and tilapia, which prey on axolotls and compete with them for food, shelter and breeding areas. The Animal Diversity Web adds that Lake Chalco was drained, and lists the species in CITES Appendix II, a list that places controls on international trade. Conservation International also gives a trend: an estimated 6,000 axolotls per square kilometer in 1998, down to 36 per square kilometer by 2014. Conservation International also describes a recent survey of 115 monitoring sites in the Xochimilco Protected Area: nets caught no axolotls, but environmental DNA, genetic traces left in the water, showed the species is still present.

Some things are going well. Conservation International reports 21 chinampa-refuges, traditional farm islands fitted with biofilters of wood, gravel and native plants, and credits them with cleaner water, fewer invasive fish and the return of native fish.

Categories are reviewed and can change, and the copy GBIF distributes can trail the IUCN website by some months, which is why we print the date we checked. GBIF’s copy does not give the year of the IUCN assessment, so we do not state one.