Patterns of hairless (hr) gene expression in mouse hair follicle morphogenesis and cycling

The hr (hairless) gene encodes a putative transcription factor with restric ted expression in the skin and brain. Mutations in the hr locus cause papul ar atrichia in humans and complete hair loss in mice and other mammals. To further elucidate the role of hr in skin biology, and to identify potential target cells for br regulation, we studied br mRNA localization during hai r follicle (HF) morphogenesis and cycling in normal C57BL/6J mice. In situ hybridization revealed that hr expression was present in the suprabasal cel l layers of the epidermis, whereas the basal and highly differentiated kera tinocytes of the granular layer were hr-negative. During the early stages o f HF morphogenesis, hr mRNA was detected in the developing hair peg. Later, it became concentrated in the HF infundibulum, in the HF matrix, and in th e inner root sheath (IRS), whereas the dermal papilla (DP) and outer root s heath were consistently hr mRNA-negative, During catagen, hr gene expressio n gradually declined in the regressing IRS, shortly but dramatically increa sed in the zone of developing club hair, and became up-regulated in the epi thelial cells adjacent to the DP. The co-localization of hr mRNA with the s ite of the morphological defects in mutant skin implicates hr as a key fact or in regulating basic cellular processes during catagen, including club ha ir formation, maintenance of DP-epithelial integrity, IRS disintegration, a nd keratinocyte apoptosis in the HF matrix.