Multiple Roles for Activated LEF/TCF Transcription Complexes During Hair Follicle Development and Differentiation

The study investigated the role of activated LEF/TCF transcription factor complexes in hair follicle development and differentiation using engineered mice with a β-galactosidase gene (TOPGAL) under a LEF/TCF and β-catenin inducible promoter. It was found that TOPGAL expression was stimulated by stabilized β-catenin and required LEF1/TCF3 in the skin. During embryogenesis, TOPGAL activation was transient in certain LEF1-positive cells, and while LEF1 was expressed in proliferative matrix cells, TOPGAL was co-induced with hair-specific keratin genes in hair shaft precursor cells. LEF1 and TOPGAL expression ceased during catagen and telogen but reappeared at the start of the postnatal hair cycle. TCF3 was expressed in postnatal outer root sheath and putative follicle stem cells, with TOPGAL activation dependent on β-catenin stabilization. The findings highlighted that LEF1/TCF3 was necessary but not sufficient for TOPGAL activation, indicating the presence of additional regulatory factors in the skin and underscoring the critical role of activated LEF/TCF complexes in hair development and cycling.