Genetic Switch That Controls Process Of Regeneration Uncovered

Salamanders can grow back limbs, geckos can drop their tails when threatened and grow them back, while other animals such as planarian worms, jellyfish, and sea anemones can regenerate their entire bodies after being cut in half.

Using three banded panther worms, which now represent a new model system for studying regeneration, to test the process Mansi Srivastava, Andrew Gehrke and colleagues found a section of non-coding DNA controls the activation of the master control gene early growth response, which once active controls a number of other processes by switching other genes either on or off as if it is a master power switch.

As many as 18,000 regions change in the dynamic nature of the genome during regeneration. The worm’s DNA which is normally tightly folded and compacted has to change to make new areas available for activation for this process to work; the genome physically becomes more open as there are regulatory switches in them that have to turn genes on/off.

EGR acts a master power switch for regeneration, once it is active other processes can take place, without it being active nothing can happen. Decreasing activity of this gene was found to inhibit regeneration; all the downstream genes would not turn on, so none of the other switches would work.

This gene was called EGR because when looking at its sequence it is similar to a gene being studied in humans and other animals, these human cells in a dish if stressed will express Egr right away. The question remains if humans can turn on Egr when our cells are injured why can we not regenerate as well? “The answer may be if EGR is the power switch, we may have different wiring, and EGR talking in human cells may be talking to something different in the three banded panther worms. We want to figure out these connections and apply them to other animals including vertebrates that can only do limited regeneration.” explains Srivastava.

In future work the team plans to investigate whether genetic switches activated during regeneration are the same as those used during development, and to further work towards gaining better understandings of the dynamic nature of the genome. They are also working in understanding the ways that EGR and other genes activate during the process for the worms and other species.

“About 2% of the genome makes things like proteins, we want to know what the other 98% is doing during whole body regeneration. We know that many DNA changes that cause disease are in non-coding regions, but these have been underappreciated for processes such as whole body regeneration. We have only scratched the surface looking at some of these switches, but there is another aspect of how the genome is interacting on a larger scale. It is not just how pieces open/close, and it all is important for turning genes on/off, there are multiple layers to this regulatory nature.” adds Gehrke.

“Many species can regenerate, and many can’t, but if you compare genomes across all animals most of the genes we have are also in the three banded panther worm; some of the answers likely will not come from whether genes are present, rather how they are wired/networked together, answers which can only come from the non-coding portion of the genome.” according to Srivastava.