F3  PATTERNS OF CREB AND PHOSPO-CREB EXPRESSION DURING MURINE HAIR FOLLICLE DEVELOPMENT AND CYCLING

Ahmed F., Müller-Röver S., Bull J., Chronnell C., Philpott M.P, Mckay I.A Centre for Cutaneous Research. St Bartholomew’s and the Royal London School of Medicine and Dentistry, QMW College London E1 2AT.

The Cyclic-AMP response element binding protein (CREB) family of transcription factors has been implicated in mediating  transcriptional responses to circadian rhythms. We have recently suggested that the ‘hair cycle clock’ may involve interaction between CREB and its inhibitor, inducible cAMP early repressor (ICER). We have used  immunohistochemistry (IH) to investigate the patterns of CREB and phospho CREB (P-CREB) expression during murine hair follicle morphogenesis and cycling. Staining was carried out on skin taken from mice aged 1, 5, 12, 16, 18, 20, 24 and 37 days, using either FITC or alkaline phosphatase (AP). During early follicle development (day 1) both CREB and P-CREB staining was cytoplasmic and restricted to the epidermis and epithelium of the hair peg. In all subsequent stages CREB staining was always nuclear and P-CREB, cytoplasmic. During late hair follicle morphogenesis (day 12) CREB was detected in the distal ORS whereas, P-CREB staining was absent. In catagen follicles (day 18) both CREB and P-CREB staining were detected in the ORS and secondary hair germ. In telogen follicles (day 20) CREB was restricted to the dermal papilla (DP) and possibly the sebaceous gland. In contrast P-CREB staining was restricted to the secondary hair germ. In late anagen follicles (day 37) CREB was absent and P-CREB was restricted to the bulge region of the ORS. In summary CREB and P-CREB show marked differences in expression during hair follicle morphogenesis and cycling. Restricted expression of CREB to the DP of telogen follicles and P-CREB to the bulge of late anagen follicles suggests possible roles for this family of transcription factors in control of the hair growth cycle.