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

EMBO J. 1999 Jul 1;18(13):3596-603. doi: 10.1093/emboj/18.13.3596.

Abstract

Transgenic mice that overexpress the anti-apoptotic gene bcl-xL under the control of the keratin 14 promoter have significantly shorter hair than non-transgenic littermates. The deficit in hair length correlated with a decrease in the duration of anagen, the growth phase of the hair cycle. A prolongation in telogen, the resting phase of the hair cycle, was also observed in adult animals. In the developing hair bulb, bcl-xL transgene expression was observed exclusively in the outer root sheath (ORS) cells. Bcl-xL expression enhanced the survival of ORS cells treated with apoptotic stimuli. The results suggest that preventing the apoptotic death of ORS cells during anagen leads to a more rapid termination of progenitor cell commitment/proliferation, while the increased survival of ORS cells during telogen delays 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-xL transgenic mice was substantially reversed in FGF-5-deficient mice. Thus, the production of growth inhibitory factors by ORS cells may provide a mechanism through which the hair-growth cycle is regulated by cell survival.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis / radiation effects
  • Cell Differentiation
  • Cell Division / radiation effects
  • Cell Survival / radiation effects
  • Epidermis / metabolism
  • Female
  • Fibroblast Growth Factor 5
  • Fibroblast Growth Factors / deficiency
  • Fibroblast Growth Factors / genetics
  • Fibroblast Growth Factors / physiology
  • Gene Deletion
  • Gene Expression
  • Hair / cytology
  • Hair / growth & development*
  • Hair / metabolism
  • Hair / radiation effects
  • Hair Follicle / cytology*
  • Hair Follicle / growth & development
  • Hair Follicle / metabolism
  • Hair Follicle / radiation effects
  • Male
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Phenotype
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Stem Cells / cytology*
  • Stem Cells / metabolism
  • Stem Cells / radiation effects
  • Ultraviolet Rays
  • bcl-X Protein

Substances

  • Bcl2l1 protein, mouse
  • Fgf5 protein, mouse
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-X Protein
  • Fibroblast Growth Factor 5
  • Fibroblast Growth Factors