Manipulation of outer root sheath cell survival perturbs the hair-growth cycle.
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.
Pena
J C
JC
The Gwen Knapp Center for Lupus and Immunology Research, The University of Chicago, Chicago, IL 60637, USA.
Kelekar
A
A
Fuchs
E V
EV
Thompson
C B
CB
D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D002454:Cell Differentiation; D002455:Cell Division / Q000528:radiation effects; D002470:Cell Survival / Q000528:radiation effects; D004817:Epidermis / Q000378:metabolism; D005260:Female; D051521:Fibroblast Growth Factor 5; D005346:Fibroblast Growth Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D017353:Gene Deletion; D015870:Gene Expression; D006197:Hair / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism / Q000528:radiation effects; D018859:Hair Follicle / Q000166:cytology* / Q000254:growth & development / Q000378:metabolism / Q000528:radiation effects; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010641:Phenotype; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000528:radiation effects; D014466:Ultraviolet Rays; D051020:bcl-X Protein
C494812:Bcl2l1 protein, mouse; C496450:Fgf5 protein, mouse; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein; D051521:Fibroblast Growth Factor 5; D005346:Fibroblast Growth Factors