Investigating Fingertip Regeneration in Mammals

Young mammals, and occasionally adults, can regenerate lost fingertips. This seems like a good place to learn more about the mechanisms of regeneration, gaining insight into why it is that mammals cannot replicate the feats of limb and organ regeneration exhibited by species such as salamanders and zebrafish. More importantly, researchers hope to find that it is practical to adjust human biology to allow this sort of exceptional regeneration:

If a salamander loses its leg, it can grow a new one. Humans and other mammals are not so fortunate, but we can regenerate the tips of our digits, as long as enough of the nail remains. This was first shown some 40 years ago; today researchers finally reveal why it is that nails are necessary. Working with mice, [researchers] 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. It suggests that we partly retain the regeneration mechanisms that operate in amphibians."

The nail base contains a small population of self-renewing stem cells, which sustain the nail's continuous growth. This ongoing growth depends on signals carried by the Wnt family of proteins - if this signalling pathway is disrupted, mouse nails cannot form. The team found that the same pathway is involved in the regeneration of lost mouse toe tips. 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.



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