The axolotl is sometimes called the Mexican walking fish, though it is not a fish at all. It is an amphibian and a type of salamander, and its closest relative is the tiger salamander. An axolotl lives in the water for its whole life. Axolotls are neotenic, which means they keep juvenile characteristics into adulthood, and they never go through metamorphosis and grow up to become adult salamanders. In experiments, treating axolotls with the thyroid hormones T4 or T3 can trigger complete metamorphosis, and adding iodine to their water causes the release of hormones that start the development of land-based traits. One idea is that axolotls stay in the water because their native lakes never dry up, so they never had to trade water traits for land ones. According to some experts, axolotls descended from tiger salamanders and have lived in central Mexico for only about the last 10,000 years.
Lazzaro Spallanzani (1729-1799) investigated salamander regeneration by amputating salamander tails and limbs. In 1864, 34 living axolotls were brought from Mexico to Paris, and in 1867 Auguste Duméril, a French herpetologist at the natural history museum in Paris, published the first scientific papers on regeneration in the Mexican axolotl. The first living axolotls that came to Europe in 1864 were the founder generation of a population of hundreds of thousands of axolotls bred in laboratories and zoos, and most axolotls in research labs around the world are descendants of the group brought to Paris in the 1860s. The axolotl is easy to breed in the laboratory and is the most commonly used salamander model organism in regeneration research, and the population in labs is often very inbred, so it has little genetic diversity.
The axolotl genome has about 32 billion base pairs, ten times the size of the human genome. A 2018 paper in Nature reported the sequencing and assembly of the 32-gigabase-pair axolotl genome with long-read sequencing, optical mapping and a new genome assembler called MARVEL. The genome shows a size expansion of introns and intergenic regions, largely attributable to multiplication of long terminal repeat retroelements, and the median intron size is 22,759 bp, which is 13, 16 and 25 times that of human, mouse and frog. Researchers reported that the CRISPR-Cas9 system can efficiently create mutations at targeted sites within the axolotl genome, and some individual animals treated with RNA-guided nucleases had mutation frequencies close to 100% at targeted sites.
Within hours after an amputation, a wound epithelium covers the severed edge of the limb. After an injury, a mass of cells called a blastema forms and can regrow the missing part. Within days, the wound epithelium becomes innervated, which means it gets a nerve supply, and turns into a signaling center called the apical epithelial cap. Blastema formation requires an adequate nerve supply. Blastema cells with positional information interact with each other and with stump cells so that regenerated tissues reform in the right place. Positional information in undifferentiated blastema cells of the early blastema can be reprogrammed to a more proximal location on the limb when exposed to retinoic acid. As of November 2026, a 2025 study suggests that a particular enzyme and gene work with retinoic acid to grow the right body part in the right spot. When an axolotl regrows a leg, every tissue is replaced, including skin, bone, cartilage and muscle.
When immune cells called macrophages were removed, salamanders lost their ability to regenerate a limb and instead formed scar tissue. Limb stumps that failed to regenerate without macrophages regained full regenerative capacity when amputated again after macrophage populations were replenished. Wound healing in a mammal leads to formation of scar tissue and does not progress to a blastema, while in axolotls wound healing eventually restores normal skin architecture rather than forming a scar. Scarring prevents tissue from regenerating, so finding out how and why axolotls do not scar could unlock human tissue regeneration. Genes that direct the growth of organs and limbs during development are silenced in adult people, but in axolotls they may be activated again after an injury.
An axolotl can regrow a lost leg in a few weeks to months, and it can also regrow hearts and parts of the brain. Salamanders can regenerate limbs, tails, retina and spinal cord, along with some sections of the heart and brain, during any stage of their life cycle. Adult mammalian regeneration in most organs and appendages is limited, while vertebrates such as zebrafish and salamanders can regenerate various organs and body parts. A tiger salamander regenerates a limb in 155 to 180 days, while a juvenile axolotl takes approximately 40 to 50 days. In general, smaller larval salamanders regenerate faster than terrestrial salamanders, and as a salamander gets older its ability to regenerate decreases, but old salamanders still regenerate missing or damaged tissues.
In the wild, axolotls come from lakes and wetlands in southern Mexico City, in Mexico, and they once lived in a series of lakes in the Mexican Central Valley. The Xochimilco-Chalco basin was once about 200 square kilometers of marshes, swamps and lagoons, and it was greatly reduced when drainage projects were completed. Urbanization and pollution of their lakes are the biggest threats to axolotls. Fish put into the waterways, such as tilapia and carp, compete with axolotls for food and eat their young. As of November 2026, the IUCN Red List lists the axolotl as Critically Endangered, and an IUCN assessment found only 50 to 1,000 axolotls left in the wild. The number of wild axolotls is decreasing. In 2025, scientists released 18 captive-bred axolotls into artificial wetlands near Mexico City. Farmers are increasingly using traditional farming methods, free of pesticides and fertilizers, to help conserve axolotls.
Words to know
- neotenic: keeping young traits
- blastema: mass of cells
- macrophages: immune cells
- epithelium: covering layer
- genome: all its genes
