It is well known that lizards can regenerate even if their tails are cut off, but there is another species on Earth with extraordinary regenerative abilities that is known as the "regeneration champion". It is the amphibian salamander. Salamanders are not only feet, but even the eyes, brain, heart and other organs can restore their original state on their own, but also can be regenerated repeatedly.
Scientists are fascinated by the salamander's strange regenerative power, but on the other hand, it is considered a "creature outside common sense", and many of the mechanisms are still a mystery.
Four years ago, the salamander's secret to subverting biological common sense was revealed. The secret that controls the resurrection of the salamander is discovered in the "red blood cells".
The red blood cells of mammals are specifically responsible for transporting oxygen, while the red blood cells of salamanders are likely to have a "time back" effect on cells near the wound, thus reshaping the body again.
So, how exactly is the unique regeneration of salamanders carried out?
The ability to regenerate beyond common sense
It takes about 5 months for salamanders to lose their legs, and it takes about 1 month for some heart defects to regenerate without scars. In addition, the function of the feet and eyes can also be restored. Moreover, it has the function of being able to regenerate multiple times in a lifetime, which is unimaginable to humans as mammals.
It is well known that lizards can regenerate even if they break their tails, but the structure of lizards and salamanders is completely different. The lizard originally had a gap in its tail, and the enemy would fall as soon as it appeared. In the process of diverting the enemy's attention, it is possible to take the action of escaping.
After the lizard's tail falls off, it grows new cartilage, shaped like a stick, used to maintain balance in the body, which is the ability of the lizard to acquire during evolution.
On the other hand, there are no pre-designed shedding sites in the salamander's body, and the wound will produce new tissue. It is unclear whether this amazing regenerative power was originally possessed by other creatures, or whether only salamanders suddenly acquired it during evolution.
If we can figure out this "unique regeneration mechanism", we may be able to apply it to human regenerative medicine, from all methods, to approach the regeneration system of salamanders.
Pepper fish
What are the "stem cells" that uncover the secrets of regenerative power?
In fact, frogs and pepperfish, which are like salamanders, are also highly regenerative during the growth period. The key to this is the "stem cells" that are active and working in the body during development.
Biological cells start from the universal cell "fertilized egg" and are divided into "stem cells" such as bones and muscles. The stem cells of the muscles are further divided into the muscles of the palms and fingertips, etc. This is called "differentiation," and once it differentiates into muscles at specific locations in the body, the cells no longer become muscle stem cells.
In the fetal period, the function of stem cells is very active, and even if the ventricles are injured, they can regenerate. However, when many organisms grow and mature, the regenerative ability of stem cells will weaken. The stem cell function of salamanders is also weakened, so why can only salamanders regenerate multiple times in their lifetime?
Damaged salamander heart, recovered after a month
The secret of the salamander regeneration system
According to "common sense", once a stem cell is differentiated, it is impossible to become a cell like the original stem cell, but this is not the case with salamanders.
For example, after a salamander's arm muscle is injured, cells differentiated from muscles in specific areas called "arms" near the wound, surprisingly, revert to "stem cell-like cells" in the muscles. The cells are like going back in time to a state before a stage.
In this state, the salamander wound can become a variety of muscles such as the muscles of the fingertips. This produces stem cell-like cells, near the wound, making mini-sized prototypes of the injured site, configuring the necessary muscle cells, and growing brilliantly. This shocking phenomenon is known as "de-differentiation."
Based on current research, it can be determined that it is the leg muscles and nerve parts of the eyes that are dedivised in salamanders. However, it can occur throughout the body, such as bones and skin.
The combination of the two mechanisms of "stem cells" and "dedifferentiation" has produced the amazing regenerative ability unique to salamanders, and detailed mechanism studies are currently being carried out.
The big discovery of biology, the red blood cells that issued the dedivision instructions?
Professor Kinfumi Chiba of the University of Tsukuba in Japan is trying to solve the mystery of the "de-differentiation" of salamander cells. Qianye believes that there are secrets hidden in the salamander genes and spends 6 years investigating the genes that work in the salamanders. The result was discovered an innate salamander gene called "Newtic1" that no other animal had.
Referring to the naming of the gene, Chiba replied: "First of all, because it was the first gene to be discovered, it was combined with the English word 'newt' for salamander and named 'Newtic1'. I expect Newtic1 to play a key role in regeneration. ”
Chiba used a laser microscope to photograph how salamander wounds were regenerating, and a month later, he found that the actively regenerated parts were concentrated with the protein produced by Newtic1 (Newtic1 protein). He then stereoscopically observed the Newtic1 protein like a rubber band around the nucleus.
What exactly is this cell? Through detailed observation, Qianye locked in an answer — "red blood cells."
In mammals, including us humans, red blood cells are supposed to be specialized in transporting oxygen and have nothing to do with body regeneration, but a closer look reveals that the red blood cells of salamanders have a "nucleus," which is not found in human red blood cells, and they produce all sorts of things. This is a discovery that subverts common sense in biology.
Referring to this situation, Qianye said: "It was really unexpected, the red blood cells are actively secreting something, a factor related to regeneration. I don't think it was unexpected, but a story that no one had imagined before. ”
Chiba Pro-Wen
How is the dedivision switch turned on?
Qianye Parent wen carefully studied the red blood cells of salamanders and found that there are at least 10 important proteins related to regeneration. A closer look at the Rubber Band-like Newtic1 protein around the red blood cells revealed that it was small particles. Qianye already had the script of salamander regeneration in her mind.
After the red blood cells in the salamander reach the wound, the regeneration-related proteins enter the particles made by Newtic1. These particles act as "porters", releasing regeneration-related proteins to necessary sites outside the red blood cells. This opens the dedivision switch, supporting the salamander's unique regenerative ability.
Although Chiba's reasoning is still in the hypothetical stage, the amazing regenerative ability that researchers have been catching up with has begun to appear.
Chiba also found that newtic1 picked out substances related to regeneration from red blood cells, humans also have. If that's the case, the salamander's surprising structure should play a role in regenerative medicine for us humans.
Small granular Newtic1 protein
"Our researchers hope to demonstrate the hypothesis of a salamander regeneration system and in the future find out the detailed formulation of the substances carried out by Newtic1 and the time they are delivered to the regeneration site to find out why humans have the same substance but cannot regenerate like salamanders, and how we can do this." We also want to establish a medical technology that uses ointments, injections or intravenous drips to deliver substances needed for regeneration to the wound. ”
On the other hand, whether this amazing regenerative ability is beneficial to salamanders is still a question.
As mentioned earlier, it takes more than 5 months for the salamander's lost foot to regenerate, which is almost of no help in escaping from predators, as it is very likely that the salamander will be eaten by the enemy before it is reborn. That is to say, this regenerative ability has little effect in nature.
Even humans, who have a strong ability to regenerate during the fetal period, lose this ability when they grow out of their mother's belly It is believed that the evolutionary process made it more advantageous for humans to leave scars and close wounds on land.
So, how do salamanders gain this regenerative ability? It's hard to imagine.
Newtic1
Genome-wide analysis deciphers the secrets of regenerative capabilities
While some of the secrets of the salamander's regenerative abilities have been uncovered, the latest research is also exploring those secrets through "whole genome analysis."
The Amphibian Research Center at Hiroshima University in Japan is conducting research on the whole genome analysis of salamanders, which has a unique facility called the "Salamander Factory" with more than 1,000 salamanders.
The genome refers to all the genetic information in which genes are the blueprints of proteins, and by studying the function of parts other than genes, the aim is to find the key to the regenerative ability of salamanders.
Salamander farms raise salamanders are Iberian salamanders, one of the largest salamanders in the world, living mainly in Spain. They can produce up to 600 eggs at a time, grow rapidly, and can multiply in a short period of time, producing a large number of uniform eggs from the same parents, making it possible to effectively conduct genetic and other studies.
Genome-wide decipherment, which requires a lot of manpower, has now been completed, and all the base sequences have been figured out.
Iberian salamander
Currently, the research center has conducted detailed studies of its sequences and found the phenomenon of "reverse transcription transposons" where parts of the genome are copied and pasted to other locations. As a result of this happening so often, the salamander's genome is already more than 7 times larger than that of humans.
The repetitive part of the genome produced by the reverse transcription transposon has long been considered a useless part that has no function.
Some people say that the size of the genome of salamanders is due to the large amount of repetitive sequence junk, and the size of the genome is meaningless.
By analyzing the entire genome in detail, the Hiroshima research team is trying to uncover the secrets behind the extraordinary regenerative abilities of these creatures, for example, in search of commonalities between them.
Salamander factory
epilogue
Until now, we still don't know why salamanders have extraordinary regenerative abilities, or whether other creatures ever had this ability, but we are captivated by the axolot's mysterious mechanism.
Thanks to years of hard work by researchers, part of the mechanism behind regenerative capacity has been revealed, and it may not be long before a new regenerative medicine that has never been seen before is born.