Expression analysis of nail matrix in mouse.

Mammalian digit-tip can regenerate upon amputation1-3, like amphibians. It is unknown why this capacity is limited to the area associated with the nail3-5. Here, we show that nail stem cells (NSCs) reside in the Wnt-suppressed proximal nail matrix and that the mechanisms governing NSC differentiation are directly coupled with their ability of orchestrating digit regeneration. Early nail progenitors located distal to the NCS region undergo Wnt-dependent differentiation into nail. Upon amputation, this Wnt activation is required for nail regeneration and also for attracting nerves that promote mesenchymal blastema growth, leading to regeneration of the entire digit. Amputations proximal to the Wnt-active nail progenitors result in failure to regenerate nail/digit. Nevertheless, β-catenin stabilization in the NSC region induced their regeneration. These results establish a link between NCS differentiation and digit regeneration, suggesting a utility of the NSCs in developing novel treatments for amputees. Nail matrix cells were harvested from proximal and distal matrix region by microdissection and processed to RNA extraction and hybridization on Affymetrix microarrays. We analyzed two proximal and two distal matrix cells.