Revealed: Why Salamanders Are Never Out on a Limb

Scientists shed light this week on how the salamander, one of nature’s great oddities, is able to regrow an amputated leg.

The insight may one day help researchers to replicate the achievement among people, they hope.

All living creatures have the ability to regrow some part or parts of their body, but the salamander tops the list for regenerative agility.

Mammals like us can regenerate skin or fuse broken bones back together, but salamanders can replace a lost limb in a few weeks, regrow damaged lungs, mend a severed spinal cord and even replenish lost chunks of brain.

Until now, biologists pondering the little amphibian’s trick have generally surmised it uses “pluripotent” cells, which charge into action at the point of amputation, called a blastema.

Pluripotent cells are spectacularly versatile cells that, like human embryonic stem cells, are somehow coaxed by chemical signals into differentiating into the specific tissues that make up skin, bone, nerves, muscle and so on.

But in a paper released by the British journal Nature, scientists from the United States and Germany say the regrowth appears to happen through more humdrum, tissue-specific cells – and this is good news.

The seven researchers first took axolotls (Ambystoma mexicanum), a species native to Mexico that is widely used as a model for vertebrate development, and genetically modified them.

They added a gene from a fluorescent jellyfish that is commonly used as a telltale in lab experiments.

Cells that carry the gene glow a livid green under ultraviolet, thus giving researchers an immediate indication of the cells’ origin and progression.

Using embryonic axolotls, the researchers transplanted transgenic tissues into sites already known to develop into certain body parts, then observed how and where the cells organised themselves as the embryo grew.

They then worked on genetically modified axolotls, cutting away limbs or organs from them.

They grafted that tissue onto normal axolotls, then cut away some of it and observed what happened to the signature “green” cells as the blastema area regenerated.

What they found was that regeneration comes not through pluripotent cells, as thought, but through cells that keep a “memory” of their tissue origin.

In other words, only “old” muscle cells make new muscle cells, only “old” nerve cells make new nerve cells, only “old” skin cells make new skin cells, and so on.

The only cells that appeared to be versatile were those that made skin and cartilage. In some circumstances, these two cell types could swap roles.

The findings are important because the salamander’s magic appears to derive from tissue-specific cells, which makes it somewhat closer to mammalian processes than thought.

“I think it’s more mammal-like than was ever expected,” one of the authors, Malcolm Maden, a University of Florida professor of biology, said in a press release.

“It gives you more hope for being able to some day regenerate individual tissues in people.”

Much more work lies ahead, though, before the vision of salamander-style regeneration can be achieved for humans who have lost a hand or leg can be taken seriously.

In a commentary, also published by Nature, University of Utah neurobiologist Alejandro Sanchez Alvarado hailed the work as unveiling “a new dimension to our understanding of regeneration.”

“Like all important work, it also leaves us with questions that will probably occupy researchers for the next few years,” he said.

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