Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Cells, Cultured
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Cytoskeletal Proteins / biosynthesis*
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Cytoskeletal Proteins / genetics
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DNA-Binding Proteins / biosynthesis
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DNA-Binding Proteins / genetics
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Embryonic Induction / genetics
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Embryonic Induction / physiology
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Epidermis / embryology
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Hair Follicle / embryology*
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Hedgehog Proteins
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Keratinocytes / metabolism
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Lymphoid Enhancer-Binding Factor 1
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Mice
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Mice, Transgenic
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Morphogenesis
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Pilomatrixoma / genetics
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Pilomatrixoma / pathology
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Proteins / physiology
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Skin / metabolism*
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Skin Neoplasms / genetics*
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Skin Neoplasms / metabolism
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Skin Neoplasms / pathology
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Trans-Activators*
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Transcription Factors / biosynthesis
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Transcription Factors / genetics
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Transfection
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Tumor Cells, Cultured
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beta Catenin
Substances
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CTNNB1 protein, mouse
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Cytoskeletal Proteins
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DNA-Binding Proteins
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Hedgehog Proteins
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Lef1 protein, mouse
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Lymphoid Enhancer-Binding Factor 1
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Proteins
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Trans-Activators
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Transcription Factors
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beta Catenin