A researcher from the Northeast University discovered how the Axolotles postpone the right member in the right place. He says that this is the next step towards the reproduction of salamander’s regeneration capacities in human medical treatment.
Axolotls, with their signing smiles and their pink gills, are the Celebrities of the Salamander world. But they are more than cute: they could also hold the secret of regenerating human members.
Among biologists, axolotls are famous for their remarkable regeneration capacities which allow them to repel whole members and even organs. NOW, James MonaghanPresident of biology and professor at the Northeastern University, began to discover the secret behind the superpower of Axolotl and how it could be used to advance human regenerative medicine.
“It could help healing without a scar, but also something more ambitious, like resuming an entire finger,” explains Monaghan. “It is not outside the (possibility) kingdom to think that something greater could grow back like a hand.”
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In a Recently published articleMonaghan decided to answer a question that “turns the field for 200 years”. How does an axolotl know which part of the body reproduce? If he loses a hand, how does he know how to resume a hand as opposed to an entire arm?
Monaghan retraces this capacity, the positional memory, returning to a molecule known as retinoic acid, which is responsible for telling the cells of an axolotl which part of the body happens. Above all, retinoic acid is not a specific Axolotl molecule – humans also have it, although we mainly obtain it from our diet and skin medications like retinol.
By examining the Axolotles, Monaghan discovered that animals have a signaling gradient of retinoic acid. In the arm, for example, this means that the axolotles have more retinoic acid in their shoulders – and less of the CYP26B1 enzyme which breaks down the molecule –– and less retinoic acid in their hands. Retinoic acid acts as an index of regenerative cells, called fibroblasts, telling them what to repel and how much repel.
“The cells can interpret this signal to say:” I’m in the elbow, then I will regain my hand “or” I’m on the shoulder. I have high levels of retinoic acid, so I will then allow these cells to push the whole member, ”explains Monaghan.
Once he understood how key retinoic acid was at the signaling of the body, Monaghan began to test the limits of this system in a way that was “quite frank”, he says. By adding additional retinoic acid in the hand of an axolotl, the salamander pushed a duplicated member instead of one hand.
Understanding the regeneration signal is a major step towards the application of these lessons to humans, says Monaghan. Humans also have retinoic acid and fibroblasts, but unlike the body of the Xaxotl, where signals are sent between all these biological actors, cells of the human body simply do not listen to the same way.
When we injure an arm, our fibroblasts place collagen and start to make a scar. In the axolotls, fibroblasts listen to retinoic acid and “go up a little time”, cultivating a new skeleton.
“If we can find ways to make our fibroblasts listen to these regenerative clues, then they will do the rest,” explains Monaghan. “They already know how to make a member because, like the Salamander, they succeeded during development.”
However, there is still a lot of work to do before humans can start pushing the members. Monaghan says that understanding the signals of the regenerative system of an Axolotl is only part of the key. The next step is to understand the mechanics of the cells themselves and what retinoic acid targets inside cells.
Monaghan has already found a target: the short Homeobox gene, or Shox. When the signaling of retinoic acid has increased, the Shox has activated, indicating that the gene is extremely important for regeneration. By completely removing the Axolotl genome shox with a gene editing technique called Crispr-Cas9, Monaghan found that the Axolotles would grow very short arms with normal-sized hands.
In particular, this is exactly what happens when humans have a shox mutation, adds Monaghan.
“For regenerative biology or regenerative medicine to progress, we must understand where positional memory is and how to manipulate it and engineering,” explains Monaghan. “How to make a cell movement where you want? Changing your positional memory is essential for that.”