Axolotls' Regenerative Abilities Could Teach Scientists a Thing or Two About Medicine
Axolotls might be cute enough to feature in a wide variety of games, TV shows, and children's toy brands, but that's not all that makes them special: The species is also exceptionally good at regenerating lost limbs and organs. Thinking that these smiling salamanders might have something to teach modern medicine, researchers in Boston are unpacking the molecules responsible for axolotls' rapid regrowth. One molecule in particular could someday help heal human wounds and replace lost limbs.
The molecule is retinoic acid, according to a paper published Tuesday in Nature Communications. Human bodies make retinoic acid out of vitamin A (obtained by eating fish, dairy, and vegetables) and occasionally receive it through cosmetic retinoids, which are used to treat acne. The molecule is key to cell growth, and if too much of it is absorbed during pregnancy, it can lead to serious birth defects.
In axolotls, retinoic acid takes that role a step further. Biologists at Northeastern University have found that axolotls rely on a retinoic acid signaling gradient, which allows different concentrations of the molecule to work in various parts of the body. Their shoulders, for instance, contain more retinoic acid (and less of the enzyme CYP26B1, which breaks it down) than their palms. When an axolotl loses its arm, the retinoic acid in its shoulder tells its fibroblasts, or regenerative cells, how to build a new one.
This axolotl is regenerating an arm after an attack. Credit: HTO/Wikimedia Commons (public domain)
According to Northeastern's write-up, this discovery led the researchers to conduct experiments that were, in their words, "pretty Frankensteiny." Adding bonus retinoic acid to an axolotl's hand allowed it to grow a duplicate limb, for example.
But simply injecting a human with extra retinoic acid won't allow them to generate new body parts. Now, the researchers are working to untangle "shox," short for the "short homeobox gene." This gene activates whenever retinoic acid signaling increases in an axolotl's body, suggesting that shox plays a part in limb regeneration. Indeed, removing shox from an axolotl's genome caused it to grow "very short arms," albeit with normal-sized hands.
Understanding how retinoic acid and shox collaborate will be the next step toward wielding axolotl insights in human medicine.
"If we can find ways of making our fibroblasts listen to these regenerative cues, then they'll do the rest," said biologist and study co-author James Monaghan. "They know how to make a limb already because, just like the salamander, they made it during development."
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