Study: Human gene thwarts regeneration in zebrafish

SAN FRANCISCO, Nov. 18 (UPI) -- Researchers often look to amphibians and insects, as well as whales and dolphins, for secrets of regeneration -- the ability to heal quickly and even regrow entire limbs.

Of course, humans have regenerative abilities too -- they're just not as powerful. The reason, a new study suggests, likely has something to do with our genetic battle with cancer.

Tumors are nothing but cell regeneration gone amok. Researchers at the University of California, San Francisco say they've identified a human gene that works at preventing both good and bad regeneration, proof that our inability to regrow appendages is the price we pay for cancer prevention.

The revelation was largely thanks to a popular aquarium fish, the zebrafish, a species increasingly common in the lab.

"In the last 10 to 15 years, as regenerative organisms like zebrafish have become genetically tractable to study in the lab, I became convinced that these animals might be able to teach us what is possible for human regeneration," Jason Pomerantz, an associate professor of plastic and reconstructive surgery at UCSF, said in a press release. "Why can these vertebrates regenerate highly complex structures, while we can't?"

When Pomerantz and his colleagues transplanted the gene called human tumor suppressor ARF (or more simply, the Arf gene) into the genomes of zebrafish, the fish lost their regenerative abilities.

Mammals boast a number of cancer-prevention genes, which in addition to curtailing tumor growth also play an important role in early tissue formation. But the Arf gene is unique to humans.

When the Arf gene was spliced into the DNA of zebrafish, researchers noticed no significant changes in tissue formation or the fishes' ability to repair superficial injuries. But when researchers cut of the fishes' tails, the gene kicked into gear. Its activation prevented the fish from regrowing the tail.

"It's like the gene is mistaking the regenerating fin cells for aspiring cancer cells," said Pomerantz. "And so it springs into action to block it."

Pomerantz says the gene could be important in various healing and anti-aging therapies. By suppressing the Arf's genetic pathway, doctors might be able to regrow organs from stem cells more effectively. But suppressing Arf could also encourage tumor growth.

"The ratio of risk and benefit has to be appropriate," Pomerantz said. "For instance, there are certain congenital diseases that cause craniofacial deformities so severe that the risks of such a treatment might be clinically reasonable."

The new research was published in the journal eLife.