Jan 27, 2022 - Science

Scientists coax frogs' cells into regrowing limbs

Frog legs

Photo: Murugan et al., Science Advances 2022

A cocktail of compounds can coax an African clawed frogs' cells to regrow a hind limb, researchers reported this week.

Why it matters: The approach could inform efforts to regenerate limbs in other animals and reveal how biological signals guide the fate of cells.

How it works: Scientists placed a silicone cap containing five different chemical compounds that are found in the embryonic environment over the wound where a frog's leg was amputated.

  • They removed the cap after 24 hours and returned the frogs — which have the ability to regenerate limbs when they are tadpoles but lose it as they become adults —to live their tank lives for the next 18 months.
  • After about four months, frogs treated with the device and compounds began to regrow new limbs, eventually with bones, nerves, muscles and toes. (Those with just the device also started to regrow, cued by the physical pressure from the device, but never to the same extent. Those without either the device or the compounds grew short spikes.)

Yes, but: It wasn't a perfect limb. It didn't have nails and the webbing between the toe projections was still abnormal.

  • Future research might look at the effect of longer exposure to the compounds, trying a different cocktail or periodically reapplying the device to the wound. And then there is the challenge of trying to regrow limbs in mammals.
  • Limbs are very complex — the cells and genes that make them aren't fully understood, says Michael Levin, an author of the study published in Science Advances and a biologist at the Allen Discovery Institute at Tufts University.
  • Guiding the animal's own cells with chemical signals is "a much more viable alternative for now" than micromanaging them with gene editing or gene therapy, he says.

The big picture: The study "shows us we can potentially kick-start latent pathways that once existed or were silenced through other developmental signals," says Nirosha Murugan, an associate professor at Algoma University in Ontario, Canada, and another author of the study.

  • And there could be different processes for regeneration, she says.
  • In the study, leg regrowth didn't include the same exact stages seen in normal limb development.

The bottom line: "Living systems can do a lot more than what they normally do," Levin says.

Go deeper