Manipulation of outer root sheath cell survival perturbs the hair-growth cycle

Transgenic mice that overexpress the anti-apoptotic gene bcl-x(L) under the control of the keratin 14 promoter have significantly shorter hair than no n-transgenic littermates. The deficit in hair length correlated with a decr ease in the duration of anagen, the growth phase of the hair cycle, A prolo ngation in telogen, the resting phase of the hair cycle, was also observed in adult animals. Zn the developing hair bulb, bcl-x(L) transgene expressio n was observed exclusively in the outer root sheath (ORS) cells, Bcl-x(L) e xpression enhanced the survival of ORS cells treated with apoptotic stimuli . The results suggest that preventing the apoptotic death of ORS cells duri ng anagen leads to a more rapid termination of progenitor cell commitment/p roliferation, while the increased survival of ORS cells during telogen dela ys the initiation of a new hair cycle. ORS cells produce fibroblast growth factor-5 (FGF-5), which acts in a paracrine fashion to terminate precursor cell division during anagen, The short hair phenotype of bcl-x(L) transgeni c mice was substantially reversed in FGF-5-deficient mice. Thus, the produc tion of growth inhibitory factors by ORS cells may provide a mechanism thro ugh which the hair-growth cycle is regulated by cell survival.