Scientists discover the secret of regeneration of Axolote members

Researchers at the University of Northeastern identified the key mechanism behind the remarkable ability of the Axolote to regenerate integers. This kind of salamander uses a “molecular GPS”, and has a regulatory gene that “speaks” with damaged cells.

A new one, published in Nature Communicationsreveals that the secret of regeneration of axolotes members is not producing more than one critical molecule, but in control its destruction.

Mexican axolote (Ambystoma mexicanum), a kind of salamander that does not develop in the larva phase, for a long time that scientists fascinates with their ability to regenerate membersparts of the heart, and even the spinal cord.

In the new study, a team of researchers from the University of Northeastern, led by the biologist James Monaghansolved one of the most intriguing questions of regenerative biology: how an amputated limb achieves “Knowing” exactly which parts that need to be regenerated?

“For years, we knew that the retinoic acida vitamin A derivative, is a crucial molecule that signals to the cells to ‘build a shoulder’, ”explains Monaghan, quoted by the magazine.

“But we didn’t understand Like cells in the limb stump regeneration controlled their levels with such precision To know exactly where they were on the shoulder axis by hand, ”details the researcher.

The surprising discovery of the team reveals that the positional identity of cells depends on a precise gradient of retinoic acid along the limb. This gradient is not created by the production of different amounts of retinoic acid, but by Variable rates of its destruction.

Cells in the pulse area contain high levels of an enzyme called CYP26B1which destroys retinoic acid. In contrast, shoulder cells have minimal amounts of this enzyme, allowing retinoic acid to accumulate.

This creates a chemical gradient that serves as a molecular GPS, informing the cells of their exact position along the limb.

To test their theory, the researchers performed an ingenious experience: amputated axolotes in their wrist and managed talarozolea medicine that inhibits the enzyme CYP26B1.

By preventing the destruction of retinoic acid, the chemist accumulated at high levels in the pulse area, confusing cellsand making them “thinking” that they were on the shoulder. Instead of regenerating only one hand, the cells produced an entire duplicate member.

The team also identified a Gene regulatordesignated Shoxactivated by high levels of retinoic acid.

Using genetic editing technology, the study authors eliminated this gene in axolote embryos, which resulted in animals with normal hands and fingers, but with Very underdeveloped arms and forearms.

This result confirmed that Shox specifically regulates the development of structures such as the upper arm and the forearm.

“We identified Shox as a critical instruction manual in this process“, Explice Monaghan.It is the gene that says to the developing cells to ‘build the bones of the arm and forearm’. ”

According to the researchers, what makes this discovery particularly intriguing is that Humans have the same fundamental genes than the axolotes. The difference is not in having “Regeneration genesUnique, but in the way these genes are accessed after an injury.

While human cells respond to lesions forming scar tissue, axolote cells reversed their differentiation For an embryonic state, allowing them to respond to signs of development such as retinoic acid.

“The difference is in accessibility of these genes“, Monaghan notes.“ As an active human injury genes that induce healing, in salamanders Cellular dedifferentiation: Cells return to a state similar to embryonic where they can respond to signs such as retinoic acid. ”

O ‘Saint Grail’ of Regenerative Biology It is being able to induce the formation of embryonic cells still undifferentiated in places of amputation in humans, explains Monaghan.

“Understand the minimum components of this process-molecular signs, the cellular environment and the physiological conditions in which it occurs-could allow us transform a scar into regenerative tissue“, Concludes the investigator.