Finally, we return to the question posed in the introduction.What are the common links between skin and bone? One recurringtheme is that Wnts are important and exhibit diversity in functionin both tissues. In the skin, Wnts, BMPs, and other signalingpathways are required for early patterning and for morphogenesisof the skin appendages including hair, teeth, nails, and mammaryglands (28, 29). Likewise, in bone, Wnts, BMPs, and FGFs arerequired, among other factors, for critical aspects of bonedevelopment. In early development, the overlying ectoderm playsan instructive role and secretes morphogens to the underlyingbone in the form of the apical ectodermal ridge during limboutgrowth (92, 93). In the adult, Wnt signaling is reprisedagain during tissue homeostasis and is a key regulator of thehair cycle as well as osteoblast and osteoclast regulation.Both skin and bone are home to specialized stem cell nichesthat provide a safe haven for their relevant progenitor cellpopulations. There are common transcriptional regulators ofbone and skin, such as the vitamin D receptor, whose cascadeof downstream effectors are clearly crucial in both tissues,since mutations in this gene cause profound effects in the formof irreversible alopecia as well as rickets (94). It has alreadybeen shown that hair follicle dermal papilla cells can differentiateinto adipocyte and osteogenic cells in culture (95), and further,that they can repopulate the entire hematopoietic system (96).The dermal papilla is easily identified within the skin by itsstrong expression of alkaline phosphatase, generally considereda marker of bone formation (97). Given the anatomical proximityof the two tissues, it is not beyond the realm of possibilitythat a common adult mesenchymal progenitor cell population supportsboth the skin dermis and underlying bone. Despite their phenotypicextremes of softness and hardness, future studies in skin andbone biology may reveal that they have far more in common thanmeets the eye.