Why Fingertips Might Grow Back But Entire Limbs Won’t

If a salamander or newt loses its leg, it can just grow another one. Humans aren’t so lucky. If you cut off my arm, it won’t grow back. (Note: please don’t do that.)

But back in the 1970s, scientists showed that children can sometimes regrow the tip of an amputated finger, as long as there’s a bit of nail left over and the wound isn’t stitched up. Later, we discovered that mice have the same ability. But why is the nail important, and why can’t a finger grow back without it? A new study provides an answer to this longstanding mystery. As I wrote in Nature News:

Working with mice, researchers led by Mayumi Ito at New York University have identified a population of stem cells lying beneath the base of the nail that can orchestrate the restoration of a partially amputated digit. However, the cells can do so only if sufficient nail epithelium — the tissue that lies immediately below the nail — remains.

The process is limited compared with the regenerative powers of amphibians, but the two share many features, from the molecules that are involved to the fact that nerves are necessary. “I was amazed by the similarities,” says Ito. “It suggests that we partly retain the regeneration mechanisms that operate in amphibians.”

You can find out more details about this process over at Nature. Meanwhile, you might also enjoy this long piece I posted a few months back, about whether we’ll ever regenerate limbs. It covers what happens in salamanders, why we can’t do the same, why these abilities have been so difficult for scientists to study, and whether we’ll ever be able to duplicate a salamander’s prowess to heal amputees. Here’s a taster:

Despite these hurdles, we know the basic steps that a regenerating limb must go through. After an amputation, cells from the outermost layer of skin climb over to seal the wound. At this point, humans would lay down lots of scar tissue, and that would be that. But in salamanders, the new cells transform into a structure called the wound epidermis, which sends chemical instructions to those below it. In response, nerves in the stump to start to grow again, while mature cells such as muscles and connective tissues revert to an immature mass called a blastema. This is what restores the limb. Regeneration is about taking a few steps back to take many steps forward.

“Somehow, the cells know their positions, and they’ll only regenerate what’s missing,” says Enrique Amaya, developmental biologist at the University of Manchester. If the limb is amputated at the shoulder or hip, the blastema creates the full leg. If it’s amputated at the wrist, the blastema makes just a hand and digits. As they grow and divide, the cells take up specific positions, so they know up from down, or left from right. They fashion a miniature version of the full limb, which eventually grows to full size.

The basic outline is there, but the details have been hard to fill. Why does the wound epidermis form, and what does it do to the cells beneath it? The limb won’t regenerate if the nerves inside don’t start growing, but what exactly do the nerves do? When cells in the stump rewind their fates to become a blastema, how far back to they go?