When we admire a creature like a lizard, starfish, or worm that can regenerate body parts after an injury, we’re really marveling at two qualities: these animals’ ability to regrow, and to stop regrowing. Because, in fact, a high degree of genetic precision is required to taper off growth signals that, when left unchecked, are a hallmark of cancer.
Scientists are fixated on this tightrope of regulated growth to one day help humans heal from heart attacks and other life-threatening injuries. Now, a new study run by Duke University biologists and published Tuesday in the journal Cell Stem Cell gets us one step closer to understanding regeneration by copying and pasting DNA from a fish into mouse and pig hearts.
Living organisms’ genetic code is made up of genes—regions that encode proteins—and a vast collection of DNA that does not provide the instructions to make anything. Instead, so-called noncoding regions can modulate and modify the protein outputs of genes. In zebrafish (a small minnow often studied by scientists as a model organism), regeneration depends on enhancers, which are one type of noncoding genetic element. Specific zebrafish enhancers turn on, dial up, and then taper off regrowth upon injury, and researchers wondered if those enhancers would have the same effect in other organisms.
The Duke team edited the genetic code of mice and pigs to introduce those zebrafish enhancers, then created injuries by amputating digits, fracturing bones, or injecting a toxic compound into their skeletal muscle. When injected before the time of injury or slightly after, the zebrafish enhancers got to work, changing the kinds and amount of proteins that the animals made.
In a subsequent experiment to discern how the enhancers affected cellular repair, the researchers altered a tissue growth gene and tracked how, after a mouse had a heart attack, one enhancer turned on the growth gene and then tapered it off after several weeks.
There’s a lot the researchers still don’t know about enhancers—how many genes they affect and what kind of regeneration they can and can’t promote—but they might be more widespread than previously thought, even in creatures that can’t regrow limbs. Like the end of a feel-good adventure movie, the researchers believe that mice and other mammals like humans may have had this enhancer DNA in our systems all along.
“Mammals likely possess all gene products required to regenerate an injured heart, crushed spinal cord connections, or amputated limbs,” the researchers wrote in the study. The trick, it seems, will be learning to turn these elements on.