Fingernails Hold Answers to Limb Regeneration in Humans

An international team of scientists reporting in the journal Nature has discovered a biochemical pathway that links nail growth to fingertip regeneration.

Digit regeneration in 3-week-old genetically engineered mice with blocked Wnt-signaling pathway and littermates. Left: whole-mount transparent specimen of a regenerated digit 5 weeks after amputation. Right: whole-mount alizarin red analysis. Scale bar - 500 μm (Makoto Takeo et al)

Digit regeneration in 3-week-old genetically engineered mice with blocked Wnt-signaling pathway and littermates. Left: whole-mount transparent specimen of a regenerated digit 5 weeks after amputation. Right: whole-mount alizarin red analysis. Scale bar – 500 μm (Makoto Takeo et al)

Mammals possess the remarkable ability to regenerate a lost fingertip, including the nail, nerves and even bone. In humans, an amputated fingertip can sprout back in as little as two months, a phenomenon that has remained poorly understood until now.

“Everyone knows that fingernails keep growing, but no one really knows why,” said study senior author Dr Mayumi Ito from the New York University’s School of Medicine.

Dr Ito and colleagues shed light on regenerative power in mammals, using genetically engineered mice to document for the first time the biochemical chain of events that unfolds in the wake of a fingertip amputation.

They have discovered an important clue in this process: a population of self-renewing stem cells in the nail matrix, a part of the nail bed rich in nerve endings and blood vessels that stimulate nail growth. Moreover, they have found that these stem cells depend upon a family of proteins known as the ‘Wnt signaling network’ – the same proteins that play a crucial role in hair and tissue regeneration – to regenerate bone in the fingertip.

“When we blocked the Wnt-signaling pathway in mice with amputated fingertips, the nail and bone did not grow back as they normally would,” Dr Ito said.

The scientists also found that they could manipulate the Wnt pathway to stimulate regeneration in bone and tissue just beyond the fingertip.

“Amputations of this magnitude ordinarily do not grow back,” Dr Ito said.

The results suggest that Wnt signaling is essential for fingertip regeneration, and point the way to therapies that could help people regenerate lost limbs.

Looking to the future, Dr Ito’s team now plans to study the molecular mechanisms that control how the Wnt signaling pathway interacts with the nail stem cells to influence bone and nail growth.

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Bibliographic information: Makoto Takeo et al. Wnt activation in nail epithelium couples nail growth to digit regeneration. Nature, published online June 12, 2013; doi: 10.1038/nature12214