A salty tail

Just adding sodium can stimulate limb regrowth in tadpoles

Researchers have hit on a winning recipe for regrowing limbs: Add a pinch of salt to a tailless tadpole; let sit for one hour. Yield: One perfectly formed tail, complete with nerves, muscles, blood vessels and other tissues.

RETAIL GROWTH Normally, tadpoles can regenerate an entire tail after an injury (top, with regrown tail). Blocking sodium from getting into cells prevents this regrowth (bottom). Ai-Sun Tseng and M. Levin/Tufts University

It’s not quite as simple as that, but results published in the Sept. 29 Journal of Neuroscience extend the window of time that tadpoles can regrow a tail, raising the possibility that other types of damaged tissue could be similarly regenerated after an injury. Salt’s surprise role in amphibian regeneration may ultimately lead to ways to coax human tissue into regrowing severed limbs and damaged organs. 

This kind of regeneration is exciting, says developmental biologist Michael King of Indiana University School of Medicine in Terre Haute, “because this would be the situation encountered in the event of accidental loss of digits or limbs in humans.”

Unlike adult humans, tadpoles possess the ability to completely regrow appendages if they’re injured. Children retain some of this ability: Until about age 11, humans can regrow fingers. But with age, the ability to regenerate tissue diminishes.

In the new study, researchers led by Michael Levin of Tufts University in Medford, Mass., found that tadpoles that couldn’t shuttle salt into their cells couldn’t regrow a tail, while normal tadpoles were perfectly able to.

Tadpole tails don’t grow back after a scarlike wound covering begins to form around the amputated tail, a process that is complete by about 18 hours after injury. But salt imported into cells near the wound can stimulate regeneration even after this scarlike tissue is firmly established, Levin and his team report.  

One particular salt-importing channel, called NaV1.2, was required for tail regrowth, the team found. NaV1.2 is well-known for its role in brain-cell communication and heart-cell beating, but scientists had no idea it might be important for regeneration.

A salty external environment alone isn’t enough to cause the tail to regrow. The salt has to be ushered into the cells near the wound, the team found. Although one of salt’s normal avenues into a cell is through the NaV1.2 channel, there are other ways, Levin says, which raises the possibility for simpler treatments. “It really doesn’t matter how the sodium gets in there,” Levin says.

One way to salt cells is with a small molecule called monensin that shuttles sodium into cells. A one-hour treatment with monensin could induce tail regeneration in tadpoles with wounds that had already formed scarlike tissue. “This simple signal kick-starts a remarkably complex process,” Levin says.

Further studies are needed to fully explain how the damage signal causes salt to flood into cells, and how the salt signal inside the cells causes tissue growth. What’s more, since many cells in the body depend heavily on exquisitely tuned salt levels, flooding all cells with salt, even just for an hour, might have unintended consequences.

The hope is that one day a simple salt signal might turn out to be useful in coaxing human appendages to regrow. “In tail regeneration, all studies up until now had to treat animals before wounding,” Levin says. “You can’t go to a doctor and get treated before you have your accident.”

Laura Sanders is the neuroscience writer. She holds a Ph.D. in molecular biology from the University of Southern California.

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