In his current research, there are still gaps to fill: how the CYP26B1 gradient is regulated, how retinoic acid connects to the Shox The gene and what downstream factors determine the formation of specific structures, such as the humerus or the radius bones.
From healing to regeneration
Monaghan explains that Axolotles do not have a “magic gene” for regeneration, but share the same fundamental genes as humans. “The main difference lies in the accessibility of these genes. While an injury in active men of genes which induce scars, in the salamanders Cell dedifferentiation: Cells return to an embryonic type state, where they can respond to signals such as retinoic acid. This ability to return to a “state of development” is the basis of their regeneration, “explains the researcher.
So if humans have the same genes, why can’t we regenerate? “The difference is that Salamander can react this (development) program after an injury.” Humans cannot – they only access this development path during initial growth before birth. “We had a selective pressure to close and heal,” explains Monaghan. “My dream and the dream of the community is to understand how to make the transition of the scar to blastem.”
James Monaghan.Photography: Alyssa Stone / Northeastern University
Monaghan says that, in theory, it would not be necessary to modify human DNA to induce regeneration, but intervene at the right time and the right place of the body with regulatory molecules. For example, the molecular routes which signal a cell to be located in the elbow on the pink side – and not from the thumb – could be reactivated in a regenerative environment using technologies such as CRISPR. “This understanding could be applied in therapies on stem cells. Currently, the stem cells cultivated in the laboratory do not know “where they are” when they are transplanted. If they can be programmed with specific position signals, they could integrate properly into damaged tissues and contribute to structural regeneration, such as the formation of a complete humerus, “explains the researcher.
After years of work, understanding the role of retinoic acid – studied since 1981 – is a source of deep satisfaction for Monaghan. The scientist imagines a future where a patch placed on an injury can reactivate development programs in human cells, emulating the regenerative mechanism of Salamander. Although he is not immediate, he believes that cell engineering induce regeneration is already an objective within the reach of science.
He is thinking about how axolotl had a second scientific life. “It was a dominant model a hundred years ago, then fell into disuse for decades, and now reappeared thanks to modern tools such as gene edition and cell analysis. The team can study any gene and cell during the regenerative process.
This story originally appeared on Cable EN ESPAñol and has been translated from Spanish.