How Do Axolotls Regenerate Limbs? Regrowing Body Parts

What body parts can an axolotl regrow?

The axolotl, a salamander from Mexico, has one of the most powerful regeneration abilities of any vertebrate (an animal with a backbone). It can rebuild:

• Limbs, complete with bones, joints, muscles, nerves, blood vessels and skin, and even the correct number of toes.
• The tail, including the section of spinal cord inside it.
• The spinal cord after it has been cut or crushed, restoring the ability to swim and walk.
• Parts of the heart, repairing damaged heart muscle so that it beats normally again.
• Parts of the brain, the jaw, the gills and tissues of the eye.
• Skin, which heals without scar tissue.

Many lizards can regrow a lost tail, but the new tail is a simpler copy with a rod of cartilage instead of bone. An axolotl’s regrown leg is almost identical to the original.

How does axolotl regeneration work, step by step?

Scientists divide limb regeneration into a few stages:

1. Closing the wound. Within hours, skin cells crawl over the cut surface and seal it. This special layer, the wound epidermis, sends signals that are needed for the next steps.
2. Forming the blastema. Over the following days, cells near the stump, such as connective tissue and muscle cells, lose some of their specialized features and begin to divide. They gather under the wound skin as a cone-shaped bud called the blastema.
3. Growing and patterning. The blastema grows and the cells inside it receive chemical signals that tell them where they are. Cells near the body build the upper part of the limb, and those at the tip build the hand or foot.
4. Rebuilding tissues. Cells turn back into bone, cartilage, muscle, tendon and skin. Nerves and blood vessels grow into the new limb, and it slowly reaches full size.

The whole process takes weeks in a small young axolotl and can take months in a large adult.

What makes regeneration possible?

Research over more than a century has found several key factors:

• Nerves are essential. If the nerves going into a limb are cut, the stump heals over but no new limb grows. Nerves release growth signals that keep the blastema active.
• Cells keep a memory of where they came from. Studies tracking individual cells show that most blastema cells rebuild the same type of tissue they came from: muscle-derived cells make muscle, and so on. They also “remember” their position, so a cut at the wrist regrows only a hand, while a cut at the shoulder regrows a whole arm.
• The immune response is different. In mammals, injuries lead to inflammation and scar tissue, which blocks regrowth. Experiments suggest that immune cells called macrophages help axolotl wounds heal without scarring, although scientists are still working out the details.

Scientists also study the axolotl’s huge genome, published in 2018 and about ten times the size of the human genome, to find genes that switch on during regeneration.

Are there limits to axolotl regeneration?

Yes. Regeneration is fastest and most complete in young axolotls and slows down as they age, although it never disappears entirely. Axolotls that have been forced to metamorphose into land-dwelling salamanders with hormones regenerate much more poorly.

Repeated injuries to the same spot can also lead to smaller or abnormal regrowth. Sometimes an injury produces an extra limb or extra toes. And an axolotl cannot survive losing vital organs, so it cannot regrow its whole head or heart.

Why do scientists study axolotl regeneration?

Axolotls have been bred in laboratories since the 1860s, when a group was sent from Mexico to Paris. They are easy to breed, have large embryos and can be studied throughout their lives. That makes them a model organism for understanding how limbs and organs develop.

Researchers hope that learning how axolotls avoid scarring and restart growth may one day help improve healing of wounds, spinal cord injuries and heart damage in people. That goal is still a long way off; no human treatment based on axolotl regeneration exists yet.

How does the axolotl compare with other animals that regrow body parts?

Other examples are explained in can starfish regrow their arms? and can crabs regrow their legs?.

Does regeneration help axolotls survive in the wild?

Probably. In the canals of Xochimilco, axolotls are bitten by fish, birds and even other axolotls, which often nip at each other’s limbs and gills. Being able to replace a lost leg or gill keeps an injured animal able to swim, hunt and breed.

Sadly, no amount of regeneration can protect them from polluted water and introduced fish. The wild population has collapsed, as explained in are axolotls endangered?.