De Novo hair follicle morphogenesis and hair tumors in mice expressing a truncated beta-catenin in skin.
An effector of intercellular adhesion, beta-catenin also functions in Wnt signaling, associating with Lef-1/Tcf DNA-binding proteins to form a transcription factor. We report that this pathway operates in keratinocytes and that mice expressing a stabilized beta-catenin controlled by an epidermal promoter undergo a process resembling de novo hair morphogenesis. The new follicles formed sebaceous glands and dermal papilla, normally established only in embryogenesis. As in embryologically initiated hair germs, transgenic follicles induce Lef-1, but follicles are disoriented and defective in sonic hedgehog polarization. Additionally, proliferation continues unchecked, resulting in two types of tumors also found in humans. Our findings suggest that transient beta-catenin stabilization may be a key player in the long-sought epidermal signal leading to hair development and implicate aberrant beta-catenin activation in hair tumors.
Pubmed ID: 9845363 RIS Download
Animals | Cells, Cultured | Cytoskeletal Proteins | DNA-Binding Proteins | Embryonic Induction | Epidermis | Hair Follicle | Hedgehog Proteins | Keratinocytes | Lymphoid Enhancer-Binding Factor 1 | Mice | Mice, Transgenic | Morphogenesis | Pilomatrixoma | Proteins | Skin | Skin Neoplasms | Trans-Activators | Transcription Factors | Transfection | Tumor Cells, Cultured | beta Catenin