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Uncovering the genetic elements that drive regeneration

deadpool tiny hand

It’s still growing, but it’s already bigger than Trumps….

Lose a hand or a leg? It will grow back… oh wait, it won’t, but why not? Trace our evolution — long before the shedding of gills or the development of opposable thumbs — and you will likely find a common ancestor with the amazing ability to regenerate lost body parts. There is theoretically no reason why we shouldn’t be able to regenerate, not quite like in the movie Deadpool, but come on, would you really complain at that point?

Thankfully for us, descendants of this creature, including today’s salamanders or zebrafish, can still perform the feat. But humans lost much of their regenerative power over millions of years of evolution — this is where we get extra upset with evolution, stupid evolution.

Let’s face it, we want those genes back, so researchers have built a running list of the genes that enable regenerating animals to grow back a severed tail, or repair damaged tissues. Turns out that the genes important for regeneration in these creatures also have counterparts in humans (did we hear a yay?).

The key difference might not lie in the genes themselves but in the sequences that regulate how those genes are activated during injury, which is a little easier to play around with than trying to change our genetics — especially considering people still kind of look down on that.

The study, using zebrafish — a favorite for researchers studying regeneration — found that the what regulated regeneration is called “tissue regeneration enhancer elements” or TREEs, these sequences can turn on genes in injury sites and even be engineered to change the ability of animals to regenerate.

“We want to know how regeneration happens, with the ultimate goal of helping humans realize their full regenerative potential,” said Kenneth D. Poss, Ph.D., senior author of the study.

“Our study points to a way that we could potentially awaken the genes responsible for regeneration that we all carry within us.”

To help us find our regenerative potential, the team looked for genes that were strongly induced during fin and heart regeneration in the zebrafish. A gene called leptin b was turned on in fish with amputated fins or injured hearts. Next, the team needed to find the controller for that gene, they scoured the 150,000 base pairs of sequence surrounding leptin b and identified a TREE — remember that stands for tissue regeneration enhancer elements, not the green things outside your house — roughly 7,000 base pairs away from the gene.

After finding what amounts to the genetic on/off switch the team did what anyone would — screw around with it to see what exactly it can do. After cutting the sequence down to the shortest it could be while still functioning, they found the element could be separated into two distinct parts: one that activates genes in an injured heart, and, next to it, another that activates genes in an injured fin.

Next, it was time to show off a little and by fusing these control sequences to two regeneration genes, fibroblast growth factor and neuregulin 1, which allowed them to create a transgenic zebrafish whose fins and hearts had superior regenerative responses after injury.

Finally, the researchers tested whether these TREEs could have a similar effect in mammalian systems like mice. By attaching one TREE to a gene called lacZ that produces a blue color wherever it is turned on it was shown that by borrowing these elements from the genome of zebrafish they could activate gene expression in the injured paws and hearts of transgenic mice.

The team suspects there may be many different types of TREEs: those that turn on genes in all tissues; those that turn on genes only in one tissue like the heart; and those that are active in the embryo as it develops and then are reactivated in the adult as it regenerates. Eventually, these could be combined with genome-editing technologies to improve the ability of mammals — meaning you and me — to repair and regrow damaged or missing body parts.

Long story short, it might not be too long before you can have superhero-like regenerating powers of your own. This is also why we all need to just need to learn to love genetic engineering instead of fearing it. I mean come on you aren’t going to grow a limb back normally and I can personally think of a few people who would love to have an arm or leg back.

Kang, J., Hu, J., Karra, R., Dickson, A., Tornini, V., Nachtrab, G., Gemberling, M., Goldman, J., Black, B., & Poss, K. (2016). Modulation of tissue repair by regeneration enhancer elements Nature DOI: 10.1038/nature17644

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