L4  GENES AND HAIR

Steijlen PM, van Geel M, van Steensel MAM. Department of Dermatology, University Hospital Nijmegen, The Netherlands.

Prior to the advent of molecular genetics the study of normal hair biology was purely descriptive. Little was known about the regulation of hair follicle cycling at the molecular level. Recently a number of genes involved in inherited hair diseases in man and mice have been elucidated. As it turns out the genes identified are crucial to the normal functioning of the hair follicle. For instance: X-linked hypohidrotic ectodermal dysplasia (Christ-Siemens-Touraine syndrome) was shown to be caused by mutations in the Ectodysplasin 1 (ED1) gene. The gene turned out to be novel, but recent data indicate that DOWNLESS (Dl), the ED1-receptor, is a TNF-related transmembrane protein. Interestingly, TNF is known to be involved in the regulation of apoptosis, a process that has recently been shown to be crucial for hair follicle growth. The hairless gene, a zinc-finger transcription factor that is at least partially controlled by thyroid hormone, is mutated in the disorder atrichia universalis. Affected patients lose all hair follicles during the first wave of folliculogenesis due to a dysregulation of apoptosis. It is tempting to speculate that the effects of ED1 and Dl mutations on hair growth are due at least in part to dysregulation of apoptosis. On the opposite side of the spectrum, the extremes of hair growth are also being elucidated. A particularly interesting mouse mutant is Angora (also occurring in cats, rabbits and hamsters). In Angora the Fibroblast growth factor 5 (Fgf5) gene is homozygously deleted. It seems that Fgf5 regulates the length of the anagen phase without affecting the other phases. These findings illustrate the profound impact of molecular genetics on our knowledge ofthe regulation of growth and cycling in hair follicles.