The roles of collagen XVIII and its endostatin domain in wound healing, hair follicle cycling and bone development

The study explored the impact of augmented β-catenin on embryonic hair follicle fate, focusing on its interaction with Shh and Bmp signaling pathways. Using mutant mice with active β-catenin in keratinocytes, researchers observed changes in hair follicle fate, evidenced by scaly skin and altered epidermal characteristics. The study demonstrated that β-catenin signaling, through Shh and Bmp pathways, was crucial for hair follicle fate change. Mutations in these pathways suppressed the hair follicle fate switch, highlighting their regulatory role. The findings suggested that Shh was essential for hair follicle fate expansion, while Bmp acted as an inhibitor, indicating a reaction-diffusion mechanism in hair follicle patterning.

The study demonstrated that hair follicle stem cells, marked by nestin-driven GFP, could differentiate into Schwann cells and support the repair of severed peripheral nerves in mice. These pluripotent stem cells, positive for CD34 and negative for keratin 15, were shown to enhance nerve regeneration and restore function when implanted into the gap of a severed sciatic nerve. The successful recovery of nerve function was evidenced by the restoration of normal walking ability in mice, as measured by muscle contraction and walking print analysis. This suggested that hair follicle stem cells could serve as an accessible and autologous source for regenerative medicine.

The study demonstrated that transient activation of β-catenin signalling in adult mouse epidermis was sufficient to induce new hair follicles, as evidenced by the recruitment of resting hair follicles into the growth cycle and the formation of epithelial outgrowths expressing markers of hair follicle differentiation. This was achieved through the application of 4-hydroxytamoxifen (4OHT) to transgenic mice expressing a modified β-catenin. A single application of 4OHT was as effective as repeated doses. However, continuous activation of β-catenin was necessary to maintain hair follicle tumours, as these benign tumours regressed after the cessation of 4OHT treatment. The findings suggested that adult interfollicular epidermis and sebaceous glands could be reprogrammed, but sustained β-catenin signalling was crucial for maintaining the tumour state.