The axolotl's regenerative power could be on your bathroom shelf.
Before the axolotl became Mexico's most beloved salamander, it was an Aztec god. Or, it was considered something very close to a deity during the pre-Hispanic period in the Americas. Elusive, solitary, a lover of the night. The appearance of this amphibian, with feathery gills that float in the water like restless flames and a dorsal fin that runs the length of its body, barely 30 centimeters long, isn't the only thing that makes it seem like an otherworldly being. The axolotl can rebuild tissues such as bones, muscles, and nerves. Everything grows back after being amputated. Perhaps that's why mythology has surrounded it with mystery. It's not just a marine animal; it's also a symbol of rebirth.
This surprising quality was what caught the attention of biologist James Monaghan , director of the Chemical Imaging of Living Systems Institute at Northeastern University (United States), who has spent more than two decades trying to decipher and understand why these animals have such unique regenerative capabilities that border on the miraculous. Twelve years after creating the first glow-in-the-dark axolotls thanks to retinoic acid (a derivative of vitamin A that acts on the skin as a biological GPS), the scientist has led a new study that has solved the mystery of how these animals manage to restore lost limbs.
“One of the great mysteries is how they know which part to regenerate. It's a question that's been around for more than 250 years, and we're trying to uncover its molecular basis,” Monaghan explains to EL PAÍS about the amphibian, which has been studied since 1864, when it was first brought to Europe from Mexico. The study, published in the journal Nature Communications, describes the discovery of a built-in molecular brake that limits regeneration. By deactivating it, scientists observe a phenomenon they call “superregeneration,” that is, an enhanced form of this process.
The protagonist here is an enzyme called CYP26B1 , which breaks down a vitamin A byproduct. This is a key signaling molecule that tells the limb which structures to replace. It's the same molecule used in skin serums (like retinol and tretinoin) and isotretinoin, which is used for severe acne. It also plays a key role in human embryonic development.
“By manipulating this enzyme, we made a hand behave as if it had been amputated at the shoulder. This means that regeneration can be influenced not only by genes, but also by metabolic pathways,” he says. The researchers also identified a gene called Shox, which controls bone development and, when altered, causes limbs to grow shorter.
How to identify the correct signsThe discovery, according to James Monaghan, identifies a pathway, such as retinoic acid signaling, that can be manipulated with drugs to change the fate of cells after injury. "If we can identify and manipulate the signals that drive cells into a regenerative state, we could apply this knowledge to healing in humans," the scientist says.
For Monaghan, "the genes responsible are there," they just need to understand how to reactivate them at the "right time and place." The problem is that in humans, reactivating them often leads to cancer, but in axolotls, they can "turn back cellular time after an injury." While we heal wounds with scars, axolotls reactivate the same cells that would form the scar to activate regeneration.
Geneticist Alfredo Cruz, from the Advanced Genomics Unit at Cinvestav (Mexico), believes that while local modulation of retinoic acid after an amputation could theoretically influence regeneration, he has his doubts. “Humans don't regenerate like axolotls, and although we can manipulate certain molecules, we don't have the same cellular or physiological environment as these animals. There are many factors at play,” he emphasizes.
Cruz was one of two Mexicans (and the only Latin Americans), along with his student Francisco Falcón, who worked on decoding the axolotl genome . Their contributions included analyzing small non-coding RNAs and supporting evolutionary studies. “The axolotl genome is very large, so it's like putting together a puzzle. Each study contributes a piece, and different groups focus on different molecules or pathways; in the end, everything connects,” he adds.
In Cruz's lab, they analyze certain transcription factors, while others work with genes like CYP26B. All of these paths, although seemingly distinct, according to the Mexican biologist, converge in understanding regeneration.
Monaghan and his colleagues' study was possible because the precise sequence of the genes involved is available. This allows experiments to be conducted to observe DNA expression in tissues. "It was a milestone for the entire scientific community studying regeneration," he recalls.
As in science, one answer leads to more questions. The next step is to understand what retinoic acid does. The compound affects cells to form an arm, for example, but it doesn't do all the work. "This is done by target genes that instruct cells to adopt specific properties and regenerate complex structures," Monaghan says. For now, they are working to identify those downstream genes.
The axolotl is in danger of disappearingAll of the world's pink axolotls are descended from a single founder animal collected near the still waters of Lake Xochimilco, a remnant of the ancient lakes that once covered the Valley of Mexico. The Ambystoma mexicanum species is one of 16 found in Mexico and is the most endangered . The axolotl has found refuge in laboratories around the world, while its natural habitat is disappearing.
For those who work in developmental biology, like scientist Alfredo Cruz, protecting the salamander has also become a responsibility. Although his laboratory wasn't founded with conservation goals in mind, they collaborate with the SiMiPlaneta Foundation, which supports species reintroduction projects. Between this year and next, they hope to release 1,000 axolotls in a semi-protected area in Xochimilco.
The axolotl is in danger due to the loss of its habitat. The Valley's lake area has been almost destroyed. Today, only a fraction of what it once was remains, and it is contaminated: it has been reduced to remnants, trapped between concrete, waste, and neglect. The scientist calls on laboratories around the world, which have studied the axolotl in captivity for decades, to consider how they can contribute to its preservation in the wild.
“It would be ideal if we also considered how to protect it in its natural habitat, not just in laboratories,” Cruz emphasizes, convinced that science cannot be separated from the life that inspires it.
EL PAÍS
