L-25   TRANSCRIPTION FACTORS AND HAIR GROWTH

MP Philpott Centre for Cutaneous Research. Barts and The London, Queen Marys School of Medicine and Dentistry, London UK.

The process of transcription, in which DNA produces RNA which in turn produces protein is central to the fundamental dogma of molecular biology. Because transcription plays such a central role in gene expression it is a central control point of gene regulation. The proteins that are involved in regulation of transcription are known as transcription factors. Transcription factors are key to tissue specific regulation of gene expression for example in muscle MyoD activates expression of muscle specific genes. Although it is debatable as to whether hair follicle specific transcription factors exist an increasing number of transcription factors have been identified in developing and adult hair follicles and as a result of transgenic mouse studies have been implicated in many aspects of hair follicle biology. Shh signalling in mammals is transduced via the Gli family of transcription factors Gli1, Gli2, and Gli3. Recent data strongly suggests that Gli2 plays a major role in hair follicle development. Moreover, both Gli1 and Gli2 have also been strongly implicated in the development of BCC. Beta-catenin is involved in both cell adhesion as well as functioning as a transcription factor. The transcriptional activity of beta-catenin is closely regulated by the activity of Wnt proteins. Likewise, the transcription factor LEF-1 also interacts with b-catenin and both beta-catenin and LEF-1 have been strongly implicated in regulation of hair follicle development and stem cell fate. The Myc superfamily of transcription factors have been strongly implicated in the regulation of cell proliferation, differentiation and apoptosis. Moreover, c-Myc has been proposed to regulate epidermal stem cells fate. In human hair follicles c-Myc is expressed in the bulge and in transgenic mice c-Myc overexpression de-synchronises the murine hair cycle and is reported to drive hair follicle stem cells towards a sebaceous gland phenotype. In conclusion the role of a number of transcription factors in regulating aspects of hair follicle biology have been dissected. However, many questions remain to be answered including what regulates the regulators? The transcriptional regulation of hair follicle cell fate and finally the role of transcription factors in the paradoxical action of androgens in hair growth.