Figure 1.

Different stages of skin appendage development. Stage 0 starts with the formation of a single layer of basal keratinocytes, which are multipotent cells. In stage 1, areas of thickening epithelium appear— known as hair placode that will end up hair follicles (HFs). The main trigger behind the formation of placodes is frequent interactions between mesenchymal cells and the epithelium. Stage 2 is associated with the extension of the hair placode downward toward the dermis. At the same time, dermal fibroblasts (Fbs) attract and create an aggregation below the placode condense as a result of an epithelial signal from the placode. During stage 3, a dermal message from the dermal aggregation induces the proliferation of the placode cells, which, in turn, surround the dermal aggregation that ultimately develops into the dermal papilla (DP). In stage 4, subsequent growth and differentiation of the epithelial cells lead to the development of the mature hair shaft. Also, the DP becomes more compact and is fully engulfed by the growing HF cells. While the sebaceous gland is evident alongside the HF, the eccrine gland begins as a basal layer bud. In stage 5, the hair shaft tip invades the hair canal. Furthermore, the swear gland lengthens and arranges in a coil.