Wnt activation in nail epithelium couples nail growth to digit regeneration

• Published in: Nature (London) Vol. 499; no. 7457; pp. 228 - 232
• Main Authors: Takeo, Makoto, Chou, Wei Chin, Sun, Qi, Lee, Wendy, Rabbani, Piul, Loomis, Cynthia, Taketo, M. Mark, Ito, Mayumi
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 11.07.2013; Nature Publishing Group
• Subjects: 631/136/532/489; 631/532/489; 631/80/86; Amputation; Animals; beta Catenin - genetics; beta Catenin - metabolism; Bone and Bones - cytology; Bone and Bones - metabolism; Cell Differentiation; Cells, Cultured; Cellular signal transduction; Epithelium - metabolism; Extremities - growth & development; Extremities - innervation; Extremities - physiology; Hoof and Claw - cytology; Hoof and Claw - growth & development; Hoof and Claw - metabolism; Humanities and Social Sciences; letter; Mesoderm - cytology; Mesoderm - metabolism; Mice; multidisciplinary; Nails (Anatomy); Physiological aspects; Regeneration (Biology); Regeneration - physiology; Science; Stem cells; Stem Cells - cytology; Stem Cells - metabolism; Wnt Proteins - metabolism; Wnt Signaling Pathway; United States
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/nature12214

Nail stem cells (NSCs) reside in the proximal nail matrix, and early nail progenitors undergo Wnt-dependent differentiation into the nail; after amputation, Wnt activation is required for nail and digit regeneration, and amputations proximal to the Wnt-active nail progenitors fail to regenerate, but β-catenin stabilization in the NSC region induces regeneration. Nail controlling digit regeneration Digit-tip regeneration in mice and humans is a remarkable example of mammalian organ regeneration. Nevertheless, this ability is very limited: digits never regenerate when amputated beyond the nail. Mayumi Ito and colleagues provide new insight into this process, by showing that the mechanisms governing nail stem cell differentiation in mice are directly coupled to their ability to orchestrate digit regeneration. Nail progenitors located distal to the nail stem cell region undergo differentiation into nail in a process dependent on Wnt signalling. Wnt signalling activation is also required for nail regeneration and for attracting nerves that promote regeneration of the entire digit after amputation. The authors suggest that nail stem cells might be used for developing new treatments for amputees. The tips of mammalian digits can regenerate after amputation 1 , 2 , like those of amphibians. It is unknown why this capacity is limited to the area associated with the nail 2 , 3 , 4 . Here we show that nail stem cells (NSCs) reside in the proximal nail matrix and that the mechanisms governing NSC differentiation are coupled directly with their ability to orchestrate digit regeneration. Early nail progenitors undergo Wnt-dependent differentiation into the nail. After amputation, this Wnt activation is required for nail regeneration and also for attracting nerves that promote mesenchymal blastema growth, leading to the regeneration of the digit. Amputations proximal to the Wnt-active nail progenitors result in failure to regenerate the nail or digit. Nevertheless, β-catenin stabilization in the NSC region induced their regeneration. These results establish a link between NSC differentiation and digit regeneration, and suggest that NSCs may have the potential to contribute to the development of novel treatments for amputees.