The daily life of regenerative salamanders whose limbs and organs regrow might be a children’s bedtime story about the importance of being enterprising and carefree, but in real life, the genes of these fascinating amphibians are the envy of many scientists across the globe. world.
One of them is Professor Elly Tanaka at the Molecular Pathology Research Institute in Vienna, Austria, who has been studying salamanders for decades.
He believes the amphibious animal has the potential to open up new ways to improve the way we treat injuries in humans and is currently working to unravel the mystery as part of the EU-funded initiative RegGeneMems projectwhich is expected to be completed in 2023.
Tanaka and her team are studying the regeneration of body structures in four-legged animals and are trying to understand why it occurs in some species and not others, most notably the highly regenerative salamander, Ambystoma mexicanum, commonly called axolotl.
“Salamanders are the best regenerators of all four-legged animals and the axolotl is a species of salamander that breeds very well, but is also very easy to breed in the laboratory,” said Tanaka. in a video interview explaining her work, for which she was awarded the prestigious Ernst Schering Prize in 2017.
The axolotl cells can restore an entire organ or limb in the right proportions, and the growth time of the limbs is always similar, regardless of the amount of tissue to be replaced. A juvenile axolotl can regenerate a limb in about 40-50 days, but as salamanders age, regeneration becomes slower.
“The subject is fascinating in an almost magical way: How a salamander can regrow an entire leg in the right shape and with nerves, muscles and bones is amazing,” Dr. Jan-Michael Peters, Executive Scientific Director at the Institute of Vienna Molecular Pathology Research, said in the same video presentation.
How do salamanders regrow limbs?
The main mystery Tanaka is trying to decipher is how the amputation of a salamander’s limb prompts its genome to start the development process from scratch.
Tanaka’s strategy was to first understand which are the most important cells that undergo the regeneration process, and then label them and see them in action and interact.
The fact that salamanders can regenerate limbs has been known since the 18th century. But what underlies this regeneration at the molecular level has long been a mystery.
As part of the RegGeneMems project, Tanaka’s lab team has now shed light on the intriguing process.
He identified the group of stem cells responsible for complex regeneration and the lesion-sensitive signals that initiate their proliferation.
Research indicates that salamanders use virtually the same molecular mechanisms used during early limb development, instead of specific cells, such as fibroblasts in the case of humans, which repair – not regenerate – our wounds.
In other words, salamander cells are capable of zeroing, specializing and starting from scratch. They are therefore flexible enough to become bones, ligaments, tendons or cartilages and also smart enough to grow an exact replica.
Tanaka also found some crucial factors that contribute to cell arrangement after an amputation, as well as the different groups of cells that are produced at different sites in the limb that together promote favorable conditions for the damaged limb to grow.
For example, the types of cells that function in the back and front of a limb are different and appear to work in concert to achieve flawless regeneration.
What does this mean for humans?
Tanaka doesn’t expect human cells to behave exactly like salamanders do, but he hopes his team can create a group of human stem cells that can regenerate in the same way as the salamander.
“Our goal is to understand how a successful example of regeneration works in order to know how to promote regeneration in non-regenerative settings,” he explained.
Specifically, he hopes this knowledge will help scientists design adult-sized tissues to replace damaged ones. For people with extensive burns or other serious injuries, this could be life changing.
Tanaka received the European Molecular Biology Organization (EMBO) Women in Science Award for her pioneering work in developing a molecular understanding of limb and spinal cord regeneration in 2020.
It is recognized for developing new methods to study the phenomenon, which was previously considered too complex to be understood at the cellular level.
Understanding animal biology has been instrumental in studying numerous human and animal diseases: cancer, respiratory diseases, Parkinson’s, Alzheimer’s and endocrine diseases are just some of them.