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Manipulation of outer root sheath cell survival perturbs the hair-growth cycle
J C Pena1, A Kelekar, E V Fuchs
1The Gwen Knapp Center for Lupus and Immunology Research, The University of Chicago, Chicago, IL 60637, USA.
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.
Insights
Overexpressing the anti-apoptotic gene bcl-xL in mice resulted in shorter hair by altering hair cycle phases. This suggests cell survival in the outer root sheath regulates hair growth.
Area of Science:
- Molecular Biology
- Dermatology
- Genetics
Background:
- The hair cycle involves distinct growth (anagen) and resting (telogen) phases.
- Apoptosis, or programmed cell death, plays a role in regulating cell populations during the hair cycle.
- The outer root sheath (ORS) cells are crucial for hair follicle development and function.
Purpose of the Study:
- To investigate the role of the anti-apoptotic gene bcl-xL in regulating the hair cycle.
- To determine how bcl-xL expression in ORS cells affects hair length and hair cycle duration.
- To elucidate the relationship between ORS cell survival and the production of growth-regulating factors.
Main Methods:
- Generation of transgenic mice overexpressing bcl-xL under the keratin 14 promoter.
- Analysis of hair length, anagen, and telogen durations in transgenic and wild-type mice.
- Examination of bcl-xL expression in the hair bulb and ORS cells.
- Assessment of the effect of bcl-xL overexpression on ORS cell survival under apoptotic stimuli.
- Evaluation of the impact of FGF-5 deficiency on the phenotype of bcl-xL transgenic mice.
Main Results:
- Transgenic mice overexpressing bcl-xL exhibited significantly shorter hair compared to controls.
- Hair length reduction correlated with a decreased duration of anagen and a prolonged telogen phase.
- bcl-xL was expressed in ORS cells, where it enhanced cell survival against apoptotic stimuli.
- Preventing ORS cell apoptosis during anagen accelerated the termination of progenitor cell proliferation.
- Increased ORS cell survival during telogen delayed the initiation of new hair cycles.
- The short hair phenotype was largely reversed in FGF-5-deficient mice, indicating FGF-5's role.
Conclusions:
- bcl-xL-mediated enhancement of ORS cell survival influences hair cycle dynamics.
- ORS cell apoptosis regulation is critical for timely progression through hair growth and resting phases.
- The production of growth inhibitory factors like FGF-5 by ORS cells, influenced by cell survival, provides a mechanism for hair cycle regulation.