Tcf3 and Tcf4 are essential for long-term homeostasis of skin epithelia

Nat Genet. 2009 Oct;41(10):1068-75. doi: 10.1038/ng.431. Epub 2009 Aug 30.


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

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • Cell Differentiation
  • Cells, Cultured
  • Embryo, Mammalian / cytology
  • Embryo, Mammalian / metabolism
  • Epithelial Cells / cytology
  • Epithelial Cells / metabolism*
  • Female
  • Homeostasis*
  • Male
  • Mice
  • Mice, Knockout
  • Mice, Nude
  • Nerve Tissue Proteins / deficiency
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Signal Transduction*
  • Skin / metabolism*
  • Stem Cells / cytology
  • Stem Cells / metabolism
  • TCF Transcription Factors / deficiency
  • TCF Transcription Factors / genetics
  • TCF Transcription Factors / metabolism*
  • Transcription Factor 4
  • Transcription Factor 7-Like 1 Protein
  • Wnt Proteins / metabolism
  • Wound Healing
  • beta Catenin / deficiency
  • beta Catenin / metabolism


  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • CTNNB1 protein, mouse
  • Nerve Tissue Proteins
  • TCF Transcription Factors
  • Tcf4 protein, mouse
  • Tcf7l1 protein, mouse
  • Transcription Factor 4
  • Transcription Factor 7-Like 1 Protein
  • Wnt Proteins
  • beta Catenin