Transcription Factor CTIP2 Maintains Hair Follicle Stem Cell Pool and Contributes to Altered Expression of LHX2 and NFATC1

J Invest Dermatol. 2015 Nov;135(11):2593-2602. doi: 10.1038/jid.2015.281. Epub 2015 Jul 15.


Transcription factor CTIP2 (chicken ovalbumin upstream promoter transcription factor-interacting protein 2), also known as BCL11B, is expressed in hair follicles (HFs) of embryonic and adult skin. Ctip2-null mice exhibit reduced HF density during embryonic development. In contrast, conditional inactivation of Ctip2 in the epidermis (Ctip2(ep-/-) mice) leads to a shorter telogen and a premature entry into anagen during the second phase of hair cycling without a detectable change in the number of HFs. Keratinocytes of the bulge stem cells (SCs) niche of Ctip2(ep-/-) mice proliferate more and undergo reduced apoptosis compared with the corresponding cells of wild-type mice. However, premature activation of follicular SCs in mice lacking CTIP2 leads to the exhaustion of this SC compartment in comparison with Ctip2(L2/L2) mice, which retained quiescent follicle SCs. CTIP2 modulates expression of genes encoding EGFR and NOTCH1 during formation of HFs and those encoding nuclear factor of activated T-cells cytoplasmic calcineurin-dependent 1 and LIM homeobox 2 during normal hair cycling in adult skin. The expression of most of these genes is disrupted in mice lacking CTIP2, and these alterations may underlie the phenotype of Ctip2-null and Ctip2(ep-/-) mice. CTIP2 appears to serve as a transcriptional organizer that integrates input from multiple signaling cues during HF morphogenesis and hair cycling.

Publication types

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

MeSH terms

  • Animals
  • Cell Differentiation / genetics
  • Cells, Cultured
  • Female
  • Gene Expression Regulation, Developmental*
  • Hair / growth & development
  • Hair Follicle / cytology
  • Hair Follicle / metabolism*
  • Keratinocytes / cytology
  • Keratinocytes / metabolism
  • LIM-Homeodomain Proteins / genetics*
  • Mice
  • Mice, Knockout
  • Models, Animal
  • NFATC Transcription Factors / genetics*
  • Repressor Proteins / metabolism*
  • Sensitivity and Specificity
  • Signal Transduction
  • Stem Cells / cytology
  • Stem Cells / metabolism*
  • Transcription Factors / genetics*
  • Tumor Suppressor Proteins / metabolism*


  • BCL11B protein, human
  • LIM-Homeodomain Proteins
  • Lhx2 protein, mouse
  • NFATC Transcription Factors
  • Nfatc1 protein, mouse
  • Repressor Proteins
  • Transcription Factors
  • Tumor Suppressor Proteins