The skin-related Reviews within this series focus mainly on4 variations on the theme of the epithelial cutaneous disease,since the epidermal barrier, the destruction of keratinocytesin pemphigus, viral infection of epithelial cells by HPV, andthe origins of itching all relate in some way to the epidermisor its resident cells. There is far more to the skin than theepidermis, and to consider it in isolation would be just scratchingthe surface. The dermis, home of mesenchymal cells in the skin,was not touched upon extensively in these Reviews, nor was thevast subject of developmental pathways such as Wnt signaling(reviewed in refs. 28, 29). Interestingly, in early development,undifferentiated mesenchymal cells can give rise to the fibroblastsof skin dermis, to adipocytes, to cartilage, to muscle, or tobone, suggesting that there are common themes at play in differentiationof these tissues (30). Since mesenchymal cells and signalingpathways are the primary focus of the second half of this Reviewseries, we shall now cut straight to the bone and examine whatlies beneath.