How to regrow a limb

Humans can’t grow back severed hands. Not even a long time ago, in a galaxy far, far away. Otherwise, there would be no need for that scene at the end of The Empire Strikes Back showing Luke getting a spiffy new cyborg hand.

What humans need med droids for, amphibians accomplish with ease. Adults can regrow entire limbs. Tadpoles, well, they don’t have limbs yet, but they can regrow their tails. A tail is a complex organ, with nerves, muscle, blood vessels, and the like, so it’s not like regrowing a patch of skin or something. And they can do all this in about a week.

Unless that tadpole is exposed to a little spritz of MS222.

MS222 means no new tail.

I’d heard about MS222 before. It’s often used as an anesthetic for fish, and I’d seen it mentioned from time to time as an anesthetic for crustaceans. I didn’t know how it worked, but I learned from a new paper from Tseng and colleagues that MS222 turns out to block voltage-gated sodium channels.

When I learned that, I thought, “A-ha! So that explains why it’s an anesthetic! Because voltage-gated sodium channels initiate action potentials! If you block them, your neurons stop working: they can’t spike.”

But then I thought, “Wait, what? Why should that make a difference in tail regeneration?”

It’s not obvious. Apparently, Tseng and colleagues found this out by screening a lot of chemicals on African clawed frog tadpoles (Xenopus laevis), not because they were specifically testing for anything related to sodium channels. And the dose they were using was so low that it wasn’t acting as an anesthetic or paralytic, so it wasn’t that MS222 was stopping regeneration by knocking the animal out.

From there, the team did a series of experiments aimed at tracking down which kind of sodium channel was involved in regeneration (there are several, slightly different ones). Then, they knocking out the channel with RNA interference, and showed that also blocked tail regeneration.

But it be cooler if we can take a tail that couldn’t regenerate, and make it grow back?

Oh yeah. We can.

Tadpoles can’t regrow their tails when they’re about a month and a half old. The sodium channels aren’t in the tail then. The research team added in a few new sodium channels: through the wonders of genetic manipulation, they added in a gene that’s normally found in mammalian hearts, and voila! Tails are regrowing. They tried another trick to get sodium inside the cells, and that also improved regeneration.

This is obviously exciting stuff. It suggests a whole new way to try to get at regenerating tissues. The authors say that many of the relevant pathways in tadpole regeneration are also present in mammals, although obviously the similarities aren’t perfect. Otherwise, Skywalker wouldn’t need that cyborg hand. Still, this has exciting potential for medical treatment.

I still don’t know why this got published in The Journal of Neuroscience, though. This isn’t a neuroscience paper. It just isn’t. That the ion channels involved are also present in neurons is probably the ostensible reason. But by that logic, you could just as well argue for publishing it in a muscle journal, since there’s muscle in the tail.

Reference

Tseng A, Beane W, Lemire J, Masi A & Levin M. 2010. Induction of vertebrate regeneration by a transient sodium current Journal of Neuroscience 30(39): 13192-13200. DOI: 10.1523/JNEUROSCI.3315-10.2010