In the movies, regeneration is the stuff of superheroes like Deadpool, who threw his lower body through some very awkward transitional scenes. Here, in reality, the mill is regenerated, with lizards and amphibians regrowing limbs and tails, while various worms regrow half of their entire body. How they handle it has been the subject of extensive study, and we have a good idea of the genes and processes involved. It can be said, however, that we have no clear idea of how the entire process is coordinated and designed to produce all the necessary tissues.
One step in this direction comes from a recent study that takes an unusual view of regeneration. To understand the process, the authors sequenced the genome of a worm that can regenerate after halving into two complete organisms. The worm is also part of a group that contains the closest living relatives of bilateral animals ̵
Xena coelo, what kind?
Most of the animals we know are bilateral animals with left and right sides. These include some creatures (like sea urchins), where the two sides are not so obvious. These bilateral animals also begin early in their development as three cell layers: an outer layer that forms skin and nerve tissue; a central, which forms internal structures such as muscles and bones; and an inner layer which then forms the lining of the intestine.
However, this is not the only body plan. Cnidarians, like jellyfish, seem to have complex structures that do not exactly match the organization we see in bilateral animals. Certain seaworms, however, form a group called Xenacoelomorpha which appears to be close to nearly bilateral animals. A Xenacoelomorph clearly has cells that form an outer layer, and it also has loosely packed cells in its interior that resemble those that make up muscles and bones in animals like ourselves. But it seems to have a pronounced belly; Its mouth easily allows access to the cavity that the loosely packed cells take. These surround each piece of food and digest it.
Researchers have suggested that this structure Xenacoelomorphs are probably the closest surviving relatives of bilateral animals. And the genome of one of these worms, Hofstenia miamia as described in the recent publication, seems to confirm this. The genome of Hofstenia indicates that it is more closely associated with us than jellyfish, and is most closely related to the least complex bilateral groups. What a thorough analysis of the genome means tells us something about the origins of bilateral life.
However, this analysis is not in the new paper. Mansi Srivastava, who runs the lab where most of the team worked, said Ars that scientists had previously identified almost all genes that Hofstenia transcribed into RNA. These show that the Hofstenia gene content is quite typical for other animals and is similar to that of bilaterals and other groups of animals. So, according to Srivastava, interest shifted to how these genes are used, and it needs to be analyzed how genes are activated or silenced.
With the head!
And what better way to focus on this than to take a close look at gene activity related to Hofstenia's impressive regeneration abilities, to which two complete animals are bred when a full-grown worm is bisected , To study this, researchers hacked the animals in half, waited a few hours (there were times between three hours and two days), and then tagged active sites in their genome.
For labeling, the researchers used a mobile genetic element, technically referred to as the transposon, sometimes referred to as the "jumping gene". Under the right conditions, these jumping genes move to new locations in the genome, but only if these locations are accessible. Areas where genes are not active tend to be tightly packed and are not targeted by the jumping gene. Areas where genes are active, on the other hand, have a looser and more open structure, which is an excellent target for a jumping gene.
By tracking the areas of the genome, researchers were able to keep track of where the DNA is located in order for new genes to become active. They had 18,000 different locations, many of which were probably active to facilitate regeneration. Some of them were head-specific, while others were largely active in the tail. Others were active in both halves of the body.
Subsequently, the team looked for proteins that could adhere to the DNA at these sites. It is already known that one of the proteins, EGR, is involved in wound healing in other organisms, and it appeared to adhere to the earliest sites that become active. This suggests that AGR acts as a "pioneer" that helps open the DNA structure in places close to critical genes and enable them to participate in regeneration.
And it seems that EGR is part of an ancient pathway with deep roots in animals. Planarian worms, also known for their ability to regenerate, have a version of AGR. It also appears to be one of the earliest genes that function during the regeneration process. Of course, humans have four EGR-related proteins, and we are more likely to have a limited ability to regenerate. Finding out how the activity of these proteins differs from the activity observed in distantly related animals may help explain why.
Meanwhile, these new data provide a framework for future investigations into the regeneration process. The pioneering function of EGR triggers a cascade of regulation of gene activity. At least two of the genes that adhere to it encode DNA binding regulatory proteins. Over time, this can help to give a more complete picture of the regeneration process.
Science 2019. DOI: 10.1126 / science.aau6173 (About DOIs).