Tadpole eye transplant shows new way to grow nerves

Lowering cells’ electrical charges could help replacement organs wire properly

nerve cells from an eye

POWER PLAY  Nerve cells (red) from an eye transplanted to a tadpole’s side reach out into the surrounding tissue, but they won’t stray beyond an electric fence of highly charged cells (green).

Douglas J. Blackiston

Wiring replacement organs into the body may be as easy as discharging a biological battery, new experiments with tadpoles suggest.

Scientists cut the eye from one tadpole’s head and transplanted it to another’s flank. Tweaking electrical charges in the recipient tadpole’s body cells stimulated nerve growth from the transplanted eye, researchers report December 1 in Neurotherapeutics.

The study could be an early step toward getting replacement eyes, ears and other organs to wire into a body properly, and it could possibly lead to a method for spinal cord repair.

It’s a feat scientists didn’t think was possible, says Silvia Chifflet, a cell biologist and physiologist at the Universidad de la República medical school in Montevideo, Uruguay. “We used to think that the nervous system, once severed, would not regenerate,” says Chifflet, who was not involved with the work.

Researchers in Michael Levin’s lab at Tufts University in Medford, Mass., removed the left eye from one tadpole and transplanted it to another tadpole’s body. Left alone, the eyes grew on the tadpole’s body, but they rarely sent out nerve branches known as axons. Axons are long protrusions that nerve cells use to connect with other neurons or with muscles or other cells.

When Levin’s group bathed the tadpoles in a drug that lowers the electrical charge of cell membranes, the transplanted eyes grew a veritable bush of axon branches. That finding suggests that “the issue of getting axons to grow out might be more solvable than people have expected,” says Amy Sater, a developmental biologist at the University of Houston.

Levin has previously shown that electrical signals can cause functional eyes to grow on tadpole’s tails (SN: 12/31/11, p. 5; SN Online: 2/28/13), suggesting that electricity is important in development.

All cells build up electric charges across their outer membrane. That charge, known as the membrane voltage potential, is regulated by the flow of charged ions into and out of the cell. Levin thinks that cells can tell where they are in an organism partly by measuring the electrical state of neighboring cells and building a topographical map of the area.

Levin’s group manipulated the membrane voltage of the host cells using drugs and genetic tricks. An antiparasite drug called ivermectin discharges cells’ membranes, essentially flattening out the electrical landscape. With wide-open territory, axons started to reach out in all directions. When researchers artificially charged cell membranes using a genetic trick, the highly charged membranes acted as electrical fences, penning in the axons and limiting their growth.   

“Our future goal is to sculpt the electrical topography of the environment and make nerves go where we want them to,” Levin says.

Other developmental biologists and physiologists stress that tadpoles are a far cry from adult humans and it is too early to tell whether manipulating electrical signals in other organisms will be as successful. Levin’s work “raises the possibility that someday there might be a way to regenerate lost organs, and although there is no way to know if this can be accomplished, the only chance of ever doing this is by gaining insight into the biological mechanism that underlies this process,” says Donald Ingber, a bioengineer at Harvard University.

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