Expression of ΔNLef1 in mouse epidermis results in differentiation of hair follicles into squamous epidermal cysts and formation of skin tumours

The study investigated the effects of repressing β-catenin/Lef1 signalling in mouse epidermis by expressing a ΔNLef1 transgene. Mice showed no skin abnormalities before the first postnatal hair cycle, but from 6 weeks of age, they experienced progressive hair loss and developed dermal cysts originating from hair follicles. These cysts expressed markers of interfollicular epidermis. Adult mice spontaneously developed skin tumours, mostly with sebaceous differentiation, suggesting an origin in the upper hair follicle. The transgene was expressed in the tumours, inhibiting β-catenin signalling, as shown by the absence of cyclin D1 expression, while patched mRNA was upregulated, implicating the sonic hedgehog pathway in tumour formation. The study concluded that β-catenin signalling levels determine keratinocyte differentiation into hair or interfollicular epidermis, and that ΔNLef1 overexpression can lead to skin tumours.