How do axolotls regenerate limbs and organs? This researcher has started to uncover the secret

How do axolotls regenerate limbs and organs? This researcher has started to uncover the secret A Northeastern University researcher discovered how axolotls regrow the right limb in the right place. He says it’s the next step toward reproducing the salamander’s regenerative abilities in human medical treatment. The axolotl’s smile has made it a favorite among the general public, but it could also be the key to regenerative medicine. Photo by Alyssa Stone/Northeastern University

Axolotls, with their signature smiles and pink gills, are the celebrities of the salamander world. But they are more than just cute: They might also hold the secret to regenerating human limbs.

Among biologists, axolotls are famous for their remarkable regenerative abilities that allow them to regrow entire limbs and even organs. Now, James Monaghan, biology chair and professor at Northeastern University, has begun to uncover the secret behind the axolotl’s superpower and how it could be used to advance human regenerative medicine.

“It could help with scar-free wound healing but also something even more ambitious, like growing back an entire finger,” Monaghan says. “It’s not out of the realm [of possibility] to think that something larger could grow back like a hand.”

Video by Bryce Van Laanen/Northeastern University

In a recently published paper, Monaghan set out to answer a question that “has plagued the field for 200 years.” How does an axolotl know what body part to grow back? If it loses a hand, how does it know to just grow back a hand as opposed to an entire arm?

Monaghan traces this ability, positional memory, back to a molecule known as retinoic acid, which is responsible for telling an axolotl’s cells what body part to grow back. Importantly, retinoic acid is not an axolotl specific molecule –– humans also have it, although we mostly get it from our diet and in skin medication like retinol.

Retinoic acid could be the key to the axolotl’s incredible ability to know which limb to regrow where, says James Monaghan, biology chair and professor at Northeastern University. Photo by Alyssa Stone/Northeastern University

By examining axolotls, Monaghan discovered the animals have a gradient of retinoic acid signaling. In the arm, for example, this means axolotls have more retinoic acid in their shoulders –– and less of the enzyme CYP26B1 that breaks down the molecule –– and less retinoic acid in their hands. The retinoic acid acts as a cue to the regenerative cells, called fibroblasts, telling them what to grow back and how much to grow back.

“The cells can interpret this cue to say, ‘I’m at the elbow, and then I’m going to grow back the hand’ or ‘I’m at the shoulder. I have high levels of retinoic acid, so I’m going to then enable those cells to grow back the entire limb,’” Monaghan says.

Once he understood how key retinoic acid was to the body’s signaling, Monaghan started testing the limits of this system in ways that were “pretty Frankensteiny,” he says. By adding extra retinoic acid in an axolotl’s hand, the salamander grew a duplicated limb instead of just a hand.