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.
Gat
U
U
Howard Hughes Medical Institute, The University of Chicago, Illinois 60637, USA.
DasGupta
R
R
Degenstein
L
L
Fuchs
E
E
D000818:Animals; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000096:biosynthesis* / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D004627:Embryonic Induction / Q000235:genetics / Q000502:physiology; D004817:Epidermis / Q000196:embryology; D018859:Hair Follicle / Q000196:embryology*; D053823:Hedgehog Proteins; D015603:Keratinocytes / Q000378:metabolism; D051821:Lymphoid Enhancer-Binding Factor 1; D051379:Mice; D008822:Mice, Transgenic; D009024:Morphogenesis; D018296:Pilomatrixoma / Q000235:genetics / Q000473:pathology; D011506:Proteins / Q000502:physiology; D012867:Skin / Q000378:metabolism*; D012878:Skin Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015534:Trans-Activators; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D014162:Transfection; D014407:Tumor Cells, Cultured; D051176:beta Catenin
C495267:CTNNB1 protein, mouse; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D053823:Hedgehog Proteins; C497574:Lef1 protein, mouse; D051821:Lymphoid Enhancer-Binding Factor 1; D011506:Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D051176:beta Catenin