Characterization of Lef-1 promoter segments that facilitate inductive developmental expression in skin

J Invest Dermatol. 2004 Aug;123(2):264-74. doi: 10.1111/j.0022-202X.2004.23201.x.


Lymphoid Enhancer Factor 1 (Lef-1) is an important developmental transcription factor required for the inductive formation of several epithelial-derived organs including hair follicles. Inductive expression of Lef-1 mRNA is tightly regulated during embryo development, suggesting the involvement of a highly regulated promoter. In vitro analysis of the Lef-1 gene has demonstrated the existence of at least two spatially distinct promoters with multiple transcriptional start sites that are responsive to the canonical Wnt/beta-catenin pathway. Regions of the Lef-1 promoter required for inductive regulation in vivo, however, have yet to be determined. To this end, we utilized LacZ-reporter transgenic mice to define segments of the human Lef-1 promoter capable of reproducing mesenchymal- or epithelial-restricted transcriptional patterns of Lef-1 expression during hair and vibrissa follicle development. These studies have revealed that a 110 bp Wnt/beta-catenin-responsive element, contained within a minimal 2.5 kb Lef-1 promoter, plays an important role in regulating mesenchymal, and potentially epithelial, expression during follicle development in mouse embryos. This 2.5 kb Lef-1 promoter also demonstrated inductive mesenchymal expression during postnatal anagen stage hair-follicle cycling. Additionally, analysis of Lef-1 promoter expression revealed previously uncharacterized regions of endogenous Lef-1 expression seen in the sebaceous glands of vibrissa and hair follicles in transgenic lines harboring the minimal Lef-1 promoter and additional intronic sequences. In summary, these studies have begun to dissect the transcriptional diversity of the human Lef-1 promoter during the hair/vibrissa follicle and sebaceous gland formation.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Division / physiology
  • DNA-Binding Proteins / genetics*
  • Female
  • Gene Expression Regulation, Developmental*
  • Genes, Reporter
  • Hair Follicle / cytology
  • Hair Follicle / embryology*
  • Hair Follicle / physiology*
  • Introns
  • Lac Operon
  • Lymphoid Enhancer-Binding Factor 1
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Pregnancy
  • Promoter Regions, Genetic / genetics*
  • Proto-Oncogene Proteins / metabolism
  • Sebaceous Glands / embryology
  • Sebaceous Glands / physiology
  • Transcription Factors / genetics*
  • Vibrissae / cytology
  • Vibrissae / embryology
  • Vibrissae / physiology
  • Wnt Proteins
  • beta-Galactosidase / genetics


  • DNA-Binding Proteins
  • Lef1 protein, mouse
  • Lymphoid Enhancer-Binding Factor 1
  • Proto-Oncogene Proteins
  • Transcription Factors
  • Wnt Proteins
  • beta-Galactosidase