Cut off part of an amphibian, and it'll regrow. But humans and other mammals can only regrew the very tips of our fingers and toes, if they're cut off. But the mechanism that makes that small feat happen could be the key to unlocking the secret of full limb regeneration in humans.
How come we can regrow fingertips, but not fingers? Researchers looked at mice, and discovered that stem cells beneath the nail were crucial to digit regrowth in mice, acting as coordinating centers for the regenerative processes. And that, in turn, could mean that nail stem cells could provide the key to human limb regeneration.
To learn more about humans' regenerative abilities, researchers took a look at mice. Using genetic labeling, they found that the base of the mice's nails house self-renewing stem cells — these cells enable our nails to continually grow throughout our lives. The stem cells rely on proteins in the Wnt signaling pathway, which scientists already knew to be an important player in embryonic nail and limb growth in the womb, according to The Scientist. If this signaling pathway is disrupted, nail growth stops.
By conducting toe-amputation experiments in two groups of mice, the scientists further discovered that the pathway is also involved in digit regeneration. That is, normal mice were able to regenerate their toe and toenails five weeks after amputation. But mice treated with a drug to block the pathway, and mice whose digits were amputated too far back, were unable to regrow anything.
Nature explains the biological processes nicely:
After amputation, the Wnt pathway is activated in the epithelium underlying the remaining nail and attracts nerves to the area. Through a protein called FGF2, the nerves drive the growth of mesenchymal cells, which restore tissues such as bone, tendons and muscle. Within five weeks, the digit is good as new.
However, none of this can happen if the digit is amputated too far back, and too much nail epithelium is lost. In such cases, the Wnt pathway is never activated, the nerves do not extend and the other tissues cannot regenerate.
Basically, the interactions between nail and bone tissues that spark digit regeneration cannot happen if the stem cells don't activate the signaling pathway (whether it's because there are no stem cells left or the pathway is somehow blocked).
If the same mechanisms hold true for humans (which is likely), nail stem cells may someday help scientists develop novel treatments for amputees, the researchers suggest.
Top image: Digit tip, including bone, regenerated in normal mice (left) and failed regeneration in Wnt-blocked mice (right). Via Ito Lab.