Abstract
Single-layered embryonic skin either stratifies to form epidermis or responds to Wnt signaling (stabilized beta-catenin) to form hair follicles. Postnatally, stem cells continue to differentially use Wnt signaling in long-term tissue homeostasis. We have discovered that embryonic progenitor cells and postnatal hair follicle stem cells coexpress Tcf3 and Tcf4, which can act as transcriptional activators or repressors. Using loss-of-function studies and transcriptional analyses, we uncovered consequences to the absence of Tcf3 and Tcf4 in skin that only partially overlap with those caused by beta-catenin deficiency. We established roles for Tcf3 and Tcf4 in long-term maintenance and wound repair of both epidermis and hair follicles, suggesting that Tcf proteins have both Wnt-dependent and Wnt-independent roles in lineage determination.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
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Cell Differentiation
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Cells, Cultured
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Embryo, Mammalian / cytology
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Embryo, Mammalian / metabolism
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Epithelial Cells / cytology
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Epithelial Cells / metabolism*
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Female
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Homeostasis*
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Male
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Mice
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Mice, Knockout
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Mice, Nude
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Nerve Tissue Proteins / deficiency
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism*
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Signal Transduction*
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Skin / metabolism*
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Stem Cells / cytology
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Stem Cells / metabolism
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TCF Transcription Factors / deficiency
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TCF Transcription Factors / genetics
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TCF Transcription Factors / metabolism*
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Transcription Factor 4
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Transcription Factor 7-Like 1 Protein
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Wnt Proteins / metabolism
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Wound Healing
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beta Catenin / deficiency
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beta Catenin / metabolism
Substances
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Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
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CTNNB1 protein, mouse
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Nerve Tissue Proteins
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TCF Transcription Factors
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Tcf4 protein, mouse
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Tcf7l1 protein, mouse
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Transcription Factor 4
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Transcription Factor 7-Like 1 Protein
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Wnt Proteins
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beta Catenin