Exploring the biology of the nail: An intriguing but less-investigated skin appendage

The nail is a highly keratinized structure covering the tip of the digit, and considered to have several important functions in our daily life. In recent years, as biological aspects of the nail organ have been characterized, we realize that the nail unit and the hair follicle share various biological and immunological features. In particular, development and homeostasis of the nail unit also requires intimate epithelial-mesenchymal interactions that involve signaling pathways such as Wnt. There is also a striking immunological resemblance between both appendages, since the nail matrix, like the anagen hair bulb and the bulge, was shown to present unique characteristics of an immune privileged site. On the other hand, considerable progress in identifying nail stem cells has succeeded in locating putative stem cell niches in the nail unit. In this context, it is intriguing that nail stem cells residing in the nail matrix were recently shown to possess the ability to organize the process leading to digit regeneration. Further elucidation of signaling pathways governing epithelial-mesenchymal interactions in the nail unit seems to be a key to develop a novel therapeutic tool to treat amputees using nail epithelium. However, it is at least certain that the nail unit has a promising potential for the future of regenerative medicine. This review explores the biology of the nail organ by focusing on intriguing knowledge gained from recent studies.