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Learning from regenerators · Axolotl

Small amphibian. Extraordinary power.

The axolotl is a salamander that can regrow entire limbs and repair its heart, spinal cord and parts of its brain. It has been studied for more than a century as a model of complex regeneration.

Established: supported by the published scientific literatureAmbystoma mexicanum
Illustration of an axolotl with magnified callouts for the gills, retina, limbs, heart and spinal cord.
Axolotl (Ambystoma mexicanum) with the gills, eye, limbs, heart and spinal cord highlighted. Illustration, not to scale.

At a glance

Scientific name
Ambystoma mexicanum
Group
Salamander (amphibian)
Regenerates
Limbs, gills, heart, spinal cord, parts of the brain
Why it is studied
Rebuilds complex structures made of many tissue types

Up close

Region by region, magnified.

What each highlighted part of the axolotl can do, how it does it and what the research shows.

Magnified illustration of an axolotl foot

01 Limbs

Whole limbs, rebuilt.

After a limb is lost, the axolotl regrows it completely: bone, muscle, nerves and skin, in the right shape and proportions.

What regenerates
The entire limb, from the point of amputation outwards.
How
Tissue at the stump forms a blastema of progenitor cells. Each tissue contributes its own progenitors, which largely keep a memory of where they came from: cells from cartilage rebuild cartilage, cells from muscle rebuild muscle.
Why it matters
Complex regeneration does not require cells to return to a fully pluripotent, embryo-like state, a finding with important implications for regenerative medicine.

Source: Kragl et al., 2009

Magnified illustration of an axolotl's feathery external gills

02 Gills

Gills that grow back.

Axolotls keep their larval, feathery external gills into adulthood. If the gills are damaged or lost, they can regenerate.

What regenerates
The external gills, one of several organs that amphibians can rebuild.
How
As in limb regeneration, signals from nerves appear to help start the process; nerve-mediated growth-factor (FGF) signalling has been compared across organs.
Why it is useful
Comparing how different organs start regenerating may reveal a shared, fundamental process.

Source: Yamamoto et al., 2021

Magnified illustration of an axolotl heart

03 Heart

A heart that recovers its function.

After part of the ventricle is removed, the adult axolotl heart rebuilds its muscle and recovers its pumping strength.

What regenerates
Ventricular heart muscle. In one study, contractile strength and heart rate returned close to normal within 90 days.
How
Structural recovery happened through the multiplication of heart-muscle cells (cardiomyocytes).
Why it is useful
The axolotl offers a second vertebrate model, alongside the zebrafish, for studying heart regeneration in adults.

Source: Cano-Martínez et al., 2010

Magnified illustration of an axolotl spinal cord

04 Spinal cord

A spinal cord that reconnects.

Axolotls can fully regenerate an injured spinal cord, which is why researchers call them the positive control for vertebrate spinal-cord regeneration.

What regenerates
The damaged or missing section of spinal cord.
How
Neural stem cells near the injury grow out and replay the process of spinal-cord development to replace the lost tissue.
Compared with mammals
Once development is complete, the mammalian spinal cord has very limited capacity to regenerate.

Source: Tazaki et al., 2017

Magnified illustration of an axolotl eye

05 Brain and eye

New neurons in the brain.

The brain and the retina both belong to the central nervous system. After injury to part of the adult axolotl brain, lost neurons can be replaced.

What regenerates
Several of the neuron types present before injury. The new neurons become electrically functional and respond to incoming signals.
Limits
In the same study, new neurons did not re-establish the long-distance connections present before injury, a reminder that even strong regenerators have limits.
Why it matters
Replacing the right kinds of neurons is a central aim of cell-replacement research in the mammalian nervous system.

Source: Amamoto et al., 2016

Proposed: a framework or hypothesis Dimzang is proposing and investigating

Why it matters to us.

The axolotl rebuilds structures made of many tissues at once. Understanding how its cells are instructed to rebuild, rather than scar, may help explain why adult mammals rarely mount the same response.

Our regeneration research Collaborate with us

Sources

Where this comes from.

  1. Kragl M, Knapp D, Nacu E, et al. Cells keep a memory of their tissue origin during axolotl limb regeneration. Nature. 2009;460(7251):60–65. doi.org/10.1038/nature08152
  2. Yamamoto S, Kashimoto R, Furukawa S, Sakamoto H, Satoh A. Comparing nerve-mediated FGF signalling in the early initiation phase of organ regeneration across multiple amphibian species. Journal of Experimental Zoology Part B. 2021;336(7):529–539. doi.org/10.1002/jez.b.23093
  3. Cano-Martínez A, Vargas-González A, Guarner-Lans V, et al. Functional and structural regeneration in the axolotl heart (Ambystoma mexicanum) after partial ventricular amputation. Archivos de Cardiología de México. 2010;80(2):79–86. pubmed.ncbi.nlm.nih.gov/21147570/
  4. Tazaki A, Tanaka EM, Fei JF. Salamander spinal cord regeneration: the ultimate positive control in vertebrate spinal cord regeneration. Developmental Biology. 2017;432(1):63–71. doi.org/10.1016/j.ydbio.2017.09.034
  5. Amamoto R, Huerta VGL, Takahashi E, et al. Adult axolotls can regenerate original neuronal diversity in response to brain injury. eLife. 2016;5:e13998. doi.org/10.7554/eLife.13998

Summaries are simplified for a general audience. Illustrations are artistic, not anatomical drawings.

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