Chapter 2 45 placode formation because all epithelial cells adopt a hair follicle fate during embryogenesis.18 Limiting Wnt activity may also be important to avoid skin tumor formation, which occurs in mice with overactive epidermal Wnt/β-catenin signaling. In Figure 3, the upper panels show paraffin sections of primary murine hair follicles at embryonic days 13 (undifferentiated epithelium), 14.5 (placode), 15.5 (germ), and 16.5–18.5 (hair peg). The lower panels show corresponding schematic developmental stages with intercellular signals indicated by arrows. The gray bar represents surface epithelium. E13 is the initial signal directing hair follicle formation come from the mesenchyme (gray dots) and instructs the overlying epithelium to form a placode. E14.5 denotes placode formation initiated in the epithelium. E15.5 signals from the epithelial cells induce the clustering of mesenchymal cells to form a dermal condensate (dark gray dots). Finally, in E16.5–18.5, the dermal condensate sends a second dermal message to the overlying follicular epithelial cells to induce proliferation and downward growth. In subsequent stages, the hair placode becomes visible under the microscope and downward growth is initiated. Epithelial cells in the placode will transmit a signal to the underlying mesenchyme to induce the formation of a small cluster of dermal cells, namely the dermal condensate (DC).13 The DC subsequently sends out second dermal signals to the epithelial cells in the placode to stimulate their proliferation, allowing downward growth of placodes further into the underlying dermis. The DC will be enveloped and travel downward with the epithelial structure, thereby forming the mature DP. The orientation of the follicle is defined at the peg stage. The follicle will not become fully mature until it reaches the bottom of the dermis, which is around postnatal day 6 in mice. At this stage the DP will be fully engulfed by the hair bulb at the base.12 As a whole, hair follicles are formed in a regular array.19 Smaller, secondary follicles that develop at a later stage are interspersed among primary hair follicles that develop earlier. It has been suggested that the formation of regular pattern of hair follicles