Trps1 and its target gene Sox9 regulate epithelial proliferation in the developing hair follicle and are associated with hypertrichosis

PLoS Genet. 2012;8(11):e1003002. doi: 10.1371/journal.pgen.1003002. Epub 2012 Nov 1.


Hereditary hypertrichoses are a group of hair overgrowth syndromes that are extremely rare in humans. We have previously demonstrated that a position effect on TRPS1 is associated with hypertrichosis in humans and mice. To gain insight into the functional role of Trps1, we analyzed the late morphogenesis vibrissae phenotype of Trps1(Δgt) mutant mice, which is characterized by follicle degeneration after peg downgrowth has been initiated. We found that Trps1 directly represses expression of the hair follicle stem cell regulator Sox9 to control proliferation of the follicle epithelium. Furthermore, we identified a copy number variation upstream of SOX9 in a family with hypertrichosis that significantly decreases expression of the gene in the hair follicle, providing new insights into the long-range regulation of SOX9. Our findings uncover a novel transcriptional hierarchy that regulates epithelial proliferation in the developing hair follicle and contributes to the pathology of hypertrichosis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Proliferation
  • DNA Copy Number Variations / genetics
  • DNA-Binding Proteins* / genetics
  • DNA-Binding Proteins* / metabolism
  • Epithelial Cells / cytology
  • Epithelial Cells / metabolism
  • Gene Expression Regulation, Developmental
  • Hair Follicle* / growth & development
  • Hair Follicle* / metabolism
  • Humans
  • Hypertrichosis* / metabolism
  • Hypertrichosis* / pathology
  • Mice
  • Morphogenesis
  • Mutation
  • Repressor Proteins
  • SOX9 Transcription Factor* / genetics
  • SOX9 Transcription Factor* / metabolism
  • Transcription Factors* / genetics
  • Transcription Factors* / metabolism


  • DNA-Binding Proteins
  • Repressor Proteins
  • SOX9 Transcription Factor
  • Sox9 protein, mouse
  • TRPS1 protein, human
  • Transcription Factors