How Do Axolotls Know to Grow Arms and Legs?
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Axolotls are pervasive in pop culture. These salamanders have a cute “smile” that makes them viral sensations on social media, and featured in video games like Minecraft and Pokémon.
Scientifically, axolotls present the unique opportunity to study the regeneration of multiple, complex body parts including the tail, liver, heart, and even parts of the brain. Think of how powerful it would be if humans could regenerate body parts damaged due to injury, illness, or aging. Limb regeneration is commonly studied in axolotls, and a new study published in Nature Communications uncovered a mechanism that regenerating limbs use to know whether they should develop limb segments that should be close to the body (proximal) or far from the body (distal).
Similar signals are used across the animal kingdom to tell limbs how to form proper structures. These signals form complex relationships as the limb grows out and away from the body. Most animals, including humans, grow limbs during initial development and can’t regrow them if they are lost to amputation. However, axolotls can regenerate their limbs by turning limb development signals on again. There are many studies on what the development signals are and how they interact to form the correct structures in the correct positions.
One of the signals is retinoic acid–you may also know this as an important skincare ingredient. In development, retinoic acid forms a gradient along each limb to identify what part should be the shoulder or hip versus fingers and toes. More retinoic acid is present in areas close to the body (shoulder and hip) and less retinoic acid is present in areas far away from the body (fingers and toes).
How the limb gradient is created was up for debate. The authors of the new study explored if the retinoic acid gradient of a regenerating limb was created in one of three different ways. Is retinoic acid created in areas where there is more of it? Is retinoic acid destroyed in areas where there is less of it? Or are there other interactions that should be considered? Ultimately, their results showed that retinoic acid is destroyed in a gradient-dependent manner as development progresses towards the fingers and toes.
Scientists are one small step closer to understanding limb regeneration, but in axolotls, not humans…The good news is that axolotls and humans share the genes that create these complex signaling relationships present in many animals. The genetic similarity and further regeneration research may one day enable humans to regrow limbs with the help of new medical treatments.
Additional fun fact: Mexico celebrates National Axolotl Day on February 1st every year to highlight their cultural significance. They are also the Mexican national amphibian.
Bring your axolotl sticker home today.
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