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Updated: May 24, 2026
Isolating Hair Follicle Stem Cells and Epidermal Keratinocytes from Dorsal Mouse Skin
Published on: April 29, 2016
The cell cycle regulator protein 14-3-3σ is essential for hair follicle integrity and epidermal homeostasis
Nigel L Hammond1, Denis J Headon, Michael J Dixon
1Faculty of Medical and Human Science and Faculty of Life Sciences, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK.
Abstract:
The 14-3-3σ (Stratifin; Sfn) is a cell cycle regulator intimately involved in the program of epithelial keratinization. 14-3-3σ is unique in that it is expressed primarily in epithelial cells and is frequently silenced in epithelial cancers. Despite its well-documented role as a cell cycle regulator and as a tumor suppressor, the function of 14-3-3σ in the intricate balance of proliferation and differentiation in epithelial development is poorly understood. A mutation in 14-3-3σ was found to be responsible for the repeated epilation (Er) phenotype. It has previously been shown that Sfn(+/Er) mice are characterized by repeated hair loss and regrowth, whereas Sfn(Er/Er) mice die at birth displaying severe oral fusions and limb abnormalities as a result of defects in keratinizing epithelia. Here we show that mice heterozygous for the 14-3-3σ mutation have severe defects in hair shaft differentiation, resulting in destruction of the hair shaft during morphogenesis. Furthermore, we report that the interfollicular epidermis and sebaceous glands are hyperproliferative, coincident with expanded nuclear Yap1 (Yes-associated protein 1)--a critical modulator of epidermal stem cell proliferation. We also report that hair follicle stem cells in the bulge cycle abnormally, raising important questions as to the role of 14-3-3σ in the bulge.
Insights
14-3-3σ (Stratifin) protein is crucial for hair shaft differentiation and epithelial development. Mutations cause hair loss and abnormal proliferation, impacting keratinization and stem cell regulation.
Area of Science:
- Cell Biology
- Developmental Biology
- Dermatology
Background:
- 14-3-3σ (Stratifin; Sfn) is a cell cycle regulator vital for epithelial keratinization.
- Its function in epithelial development, proliferation, and differentiation is not fully understood.
- 14-3-3σ is frequently silenced in epithelial cancers, suggesting a tumor suppressor role.
Purpose of the Study:
- To investigate the role of 14-3-3σ in epithelial development and keratinization.
- To elucidate the function of 14-3-3σ in hair follicle morphogenesis and stem cell regulation.
- To understand the consequences of 14-3-3σ mutations on epidermal homeostasis.
Main Methods:
- Analysis of mouse models with 14-3-3σ mutations (Sfn(+/Er) and Sfn(Er/Er)).
- Histological examination of skin and hair follicle structures.
- Assessment of cell proliferation markers and stem cell populations (Yap1, bulge cells).
Main Results:
- Heterozygous 14-3-3σ mutations cause severe hair shaft differentiation defects and destruction during morphogenesis.
- The interfollicular epidermis and sebaceous glands exhibit hyperproliferation.
- Expanded nuclear Yap1 and abnormal hair follicle stem cell cycling are observed in mutant mice.
Conclusions:
- 14-3-3σ plays a critical role in hair shaft differentiation and epidermal homeostasis.
- Mutations in 14-3-3σ disrupt normal proliferation and differentiation balance, affecting stem cell behavior.
- Further research is needed to clarify 14-3-3σ's specific role in hair follicle stem cells.
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