While you scar yourself from a scratch, the axolotl regrows an entire limb. This Mexican salamander has solved a problem that has tormented humanity since time immemorial: how to repair the body without simply patching it up. Its secret? A molecular orientation system based on retinoic acid that works like a GPS for cells. When an axolotl loses a limb, its cells know exactly what they need to rebuild and where to place each individual piece. A surgical precision that has fascinated James monaghan of Northeastern University, the researcher who has finally deciphered this mechanism of limb regeneration.
How the Molecular Orientation System Works
The axolotl's trick lies in a sophisticated and elegant chemical device. Retinoic acid, a derivative of vitamin A that we all know, is distributed along the body of the animal creating a precise map. In the shoulders the concentration is high, in the legs it is low. When a tissue is damaged, the cells read this chemical map and know exactly where they are.
The enzyme CYP26B1 acts as a regulator, degrading retinoic acid where it isn’t needed. When Monaghan and his team inhibited this enzyme in axolotls, the results were astonishing: the animals regenerated deformed limbs, with excess or incorrectly positioned bones. Without the right signal, the body no longer knew where it was building.
The discovery, published in Nature Communications, answers a question that has tormented biologists for over two centuries: how does an organism know what to regenerate? The answer lies in positional memory, a system of molecular coordinates that every cell carries with it.
The Shox Gene and Human Limb Regeneration
Another fundamental piece emerged by studying the gene Shox. When retinoic acid levels rise, this gene is activated, proving to be crucial for limb regeneration. By removing Shox from the axolotl genome using CRISPR-Cas9, Monaghan observed that the animals developed very short arms with normal-sized hands.
The most fascinating detail? In humans, mutations in the Shox gene cause exactly the same abnormalities. This suggests that the biological mechanism is shared between us and these extraordinary creatures.
Rebel Fibroblasts and Regenerative Medicine
We humans also have retinoic acid and fibroblasts, the cells responsible for tissue repair. The crucial difference is that our fibroblasts don’t listen to regenerative signals like axolotl fibroblasts do. When we get injured, our cells simply produce collagen and form scars. In axolotls, however, fibroblasts respond to retinoic acid by “going back in time” and rebuilding complete skeletons.
“If we could get our fibroblasts to listen to these regenerative signals, they would do the rest themselves,” Monaghan explains. “They already know how to build a limb because they did it during embryonic development.”
The road to human regenerative medicine is still long, but as I pointed out in this article, perhaps there will be no need to invent anything new: we just need to reactivate what we already have inside.
