How Do Salamanders Regrow Lost Limbs? Blastema, Positional Memory and Nerves

ByKen

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How do salamanders regrow lost limbs? The sources checked describe a process that starts at the cut surface. A review of positional memory states the capacity directly: “Salamanders, such as axolotls and newts, can regenerate complex tissues including entire limbs”. The process relies on a mass of cells called the blastema, on a memory of where each part of the limb belongs, and on nerves that carry factors into the regrowing tissue. The points below explain each part in order, and they note where the sources stop short of a full account.

Quick answer

  • A regrowth tissue forms at the wound: “the blastema (the cell mass that gives rise to the new limb)”.
  • Cells remember their position: “Thus, salamander cells interpret spatial location to direct position-specific regeneration”.
  • Nerves support the process: “peripheral nerves retract after amputation and then regrow into the blastema, secreting factors necessary for regeneration to progress”.
  • The sources do not give a full molecular map for every salamander species.

How we chose these sources

Both sources are hosted on PubMed Central. The first is titled “Positional Memory in Vertebrate Regeneration: A Century’s Insights from the Salamander Limb”, and the second is titled “Model systems for regeneration: salamanders”. Each page was opened and its article text was checked before any quote was taken. The first source covers the positional memory idea in detail, and the second covers the cellular and nerve steps in the regrowth process.

The wound forms a blastema

Regrowth starts with a tissue mass at the injury. The second source defines the term: “the blastema (the cell mass that gives rise to the new limb)”. It then explains how that mass changes: “Recent work profiling connective tissue during limb regeneration has demonstrated that these heterogeneous cells transit to an embryonic-like state that is more homogenous in the blastema”. That statement describes cells that return to a more uniform state before they build the new limb.

The second source also reports a single-cell study of the axolotl. “In fact, recent single cell RNAseq (scRNA-seq) profiling of the axolotl regenerating limb demonstrated that the majority of the blastema reverts to a limb bud-like transcriptional profile”. The phrase “limb bud-like” describes a profile similar to that of an early limb bud.

The process is not identical across species. The source contrasts two species on muscle. “In contrast, the axolotl does not exhibit muscle dedifferentiation during limb regeneration”. The same passage describes the newt. “A similarly radical manifestation of in vivo reprogramming as a response to injury also occurs during newt limb regeneration when postmitotic, multinucleated muscle cells break up into mononucleate progeny, which subsequently re-enter the cell cycle and contribute to the new appendage”. The two species therefore use different routes for muscle.

Positional memory sets the pattern

Forming a blastema is not enough by itself. The regrowing limb must also build the right parts. The first source asks the key question: “But what mechanisms ensure that an amputated limb regenerates a limb, and not a tail or unpatterned tissue?” Its answer rests on positional memory. The source explains that “An important concept in regeneration is positional memory—the notion that adult cells “remember” spatial identities assigned to them during embryogenesis”.

The memory is used during regrowth to set the structure. “Thus, salamander cells interpret spatial location to direct position-specific regeneration”. This means the cells at the cut do not simply rebuild a generic limb. They follow a plan based on where they were before the injury.

The effect of position is visible in what is regrown. “Amputating a salamander limb at any place between the body wall and hand/foot regenerates only the missing structures”. The source gives the example of the forelimb. “The axolotl forelimb has four digits, and a total of 24 skeletal elements”.

The source also explains why the salamander is a useful model. “Salamanders are informative as they possess similar tissue types to humans and regenerate at relevant size scales using evolutionarily conserved molecules”. The phrase “evolutionarily conserved molecules” indicates that some of the regrowth tools are shared across animals, although the sources do not claim that humans can do the same.

Related explainers on animal growth and body renewal are how insects molt their exoskeleton and how caterpillars turn into butterflies during metamorphosis.

Nerves support regrowth

Nerves are part of the process. “During this event, peripheral nerves retract after amputation and then regrow into the blastema, secreting factors necessary for regeneration to progress”. This statement is about the timing of nerve retraction and regrowth, and it names the nerves as a source of factors that the regrowth needs.

The source notes that regrowth is accurate in normal cases: “Although salamanders regenerate amputated limbs with high fidelity”. It also reports that removing a region changes the result, because the excised region leads to “a regenerated limb with incorrect patterning”.

Genes are also reused in the process. The second source states that “genes responsible for patterning and morphogenesis are re-activated during limb regeneration, although their precise regulation is not a complete recapitulation of embryonic development”. That means the regrowth reuses developmental genes, but not in exactly the same way as in the embryo.

Speed and species differences

The time needed to regrow a limb varies. “The speed of salamander limb regeneration varies among species and developmental stage, but is nevertheless impressive”. One example is given in the second source: a newt species “completes adult limb regeneration within less than 2 months”. That gives a sense of the time scale without saying how the timing is set.

The axolotl and the newt are the best-known examples, and the first source names them together: “Salamanders, such as axolotls and newts”. Other salamanders may follow the same general plan, but the sources do not describe each species separately.

What we could not verify

What the sources do not say

The sources do not give the complete molecular map for any salamander limb. They describe patterning and genes in general, and they do not list each signal that tells a cell where it is.

The sources do not state how a salamander decides the size of a regrown limb. The second source covers the nerve and blastema steps, but it does not describe the signal that stops growth at the correct size.

The sources do not describe whether a wild salamander regrows limbs at the same speed as a laboratory animal. They describe regeneration in model species, and the speed depends on “species and developmental stage”.

Frequently asked questions

What tissue forms first after a limb is lost?

The second source names the blastema: “the blastema (the cell mass that gives rise to the new limb)”.

Do salamanders regrow only limbs?

The first source says they regenerate more than limbs: “Salamanders are amphibians able to regenerate diverse tissues including entire limbs, large parts of their central nervous system, visual system, gills, and tails”.

How does the new limb know its shape?

Through positional memory: “Thus, salamander cells interpret spatial location to direct position-specific regeneration”.

Why are nerves important?

The second source says nerves regrow into the blastema: “peripheral nerves retract after amputation and then regrow into the blastema, secreting factors necessary for regeneration to progress”.

How fast does a salamander regrow a limb?

The speed varies: “The speed of salamander limb regeneration varies among species and developmental stage, but is nevertheless impressive”.

Sources

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