Scientists are solving the mystery of how axolotls regrow limbs
A wounded axolotl can regenerate an entire lost leg or only its pinky toe. How the mass of cells that migrate to the wound site, known as a blastema, knows exactly what's needed is a key question the new paper helps answer.
'Evidence suggests it's the access to the appropriate genes after an injury that enable them to regenerate an arm. So they can turn on those programs that built the arm in the first place,' Monaghan says, referring to the gene Shox, which initially creates and then recreates the long bones needed to make an arm or leg.
Monaghan also found an enzyme called CYP26B1 reduces the amount of retinoic acid at the site to exactly the level needed for a particular body part. It's the quantity of the retinoid that tells the cells what it is building, the researchers found. So the mass of cells capable of forming an entire arm has more than those making a hand or, at even lower amounts, a finger.
In humans as well as other animals, retinoic acid is integral to cell differentiation and growth. Its role in human development is so important that women are urged to avoid the oral acne retinoid medication isotretinoin during pregnancy so as not to interfere with natural levels—although recent research found no increased risk of birth defects or disabilities.
Rather than create the retinoic acid, the enzyme assesses current levels and reduces it to the desired amount. This was unexpected, Monaghan says, and crucial to understanding the process humans might one day use to regenerate limbs, too. Advances in gene editing could one day unlock major innovations in medical treatment. Scientists hope they could even figure out how to regrow human limbs.
Photograph By Alyssa Stone/Northeastern University Could humans one day regrow missing limbs?
Somewhere back in our evolutionary tree, humans and other mammals lost the ability to regrow severed appendages, a trade-off that comes with our more complex, higher-functioning parts. (One exception: newborn babies can regrow fingertips.)
Scientists are hopeful these regenerative capacities remain hidden in our biology. If so, 'we can learn to unlock them, potentially restoring greater regenerative potential than we currently see,' says Thomas Rando, director of the Broad Stem Cell Research Center at the University of California, Los Angeles, who was not involved in this study.
Rando believes even the manipulation of human stem cells he and others are studying may benefit from the axolotl research.
'In mammals, we rely on skin stem cells to make skin, bone stem cells to make bone, and muscle stem cells to make muscle,' he says. What isn't known is how to make these cells produce multiple tissues at once, which is necessary to regenerate a functioning limb. Learning how amphibians successfully do this could yield treatments that entice stem cells to mimic those actions.
(The ability to reverse damage to your lungs and heart is tantalizingly close.)
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