The cell-cycle regulator protein 14-3-3σ is essential for hair follicle integrity and epidermal homeostasis

14-3-3σ (Stratifin; Sfn) is a cell cycle regulator intimately involved in the programme of epithelial keratinisation. 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 tumour suppressor, 14-3-3σ’s function 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 Sfn(+/Er) mice are characterised by repeated hair loss and re-growth while Sfn(Er/Er) mice die at birth displaying severe oral fusions and limb abnormalities as a result of defects in keratinising epithelia. Here we show mice heterozygous for the 14-3-3σ mutation have severe defects in hair shaft differentiation, resulting in destruction of the hair shaft during morphogenesis. Further, we report the inter-follicular epidermis and sebaceous glands are hyperproliferative, coincident with expanded nuclear Yap1; a critical modulator of epidermal stem cell proliferation. We also report hair follicle stem cells in the bulge cycle abnormally raising important questions as to the role of 14-3-3σ in the bulge.