Abstract
The hair follicle is the only periodically and regularly regenerating organ system throughout the lifetime of the mammalian adult ; therefore, the hair follicle is the ultimate model for the study of morphogenesis, tissue remodeling, and stem cells. Many growth factors and transcription factors such as FGF, BMP, tabby/downless, EGF family, Wnt-Frizzled-β-Catenin-Lef-1, and Shh-Patched have been identified as morphogenic molecules, and some genes are directly involved in the development of skin tumors. Several genes are specifically involved in the remodeling of hair follicles. Stat3 is a downstream signaling molecule of cytokines and growth factors including EGF and HGF. Conditional targeting using the K5-Cre/loxP system allowed us to generate keratinocyte-specific Stat3 knockout mice. Comprehensive analysis of skin development as well as wound healing and hair cycling in these keratinocyte-specific, Stat3-null mice revealed that Stat3 plays pivotal roles in skin remodeling. Another typical example of the signal transduction in the hair follicle is the androgen-androgen receptor system. Human dermal papilla cells (DPC) are targets of androgens. Insulin-like growth factor-I (IGF-I) was identified as one of the androgen dependent paracrine growth factors needed for hair growth. In contrast, frontal scalp DPC inhibit the growth of follicular epithelial cells in an androgen-dependent manner. TGF-β may be involved in this growth suppression.
