Transcription Factor CTIP2 maintains hair follicle stem cell pool and contributes to altered expression of LHX2 and NFATC1

Transcription factor CTIP2 (COUP-TF-interacting protein 2), also known as BCL11B, is expressed in hair follicles of embryonic and adult skin. Ctip2-null mice exhibit reduced hair follicle density during embryonic development. In contrast, conditional inactivation of Ctip2 in epidermis (Ctip2(ep−/−) mice) leads to a shorter telogen and premature entry into anagen during the second phase of hair cycling without a detectable change in the number of hair follicles. Keratinocytes of the bulge stem cells niche of Ctip2(ep−/−) mice proliferate more and undergo reduced apoptosis than the corresponding cells of wild-type mice. However, premature activation of follicular stem cells in mice lacking CTIP2 leads to the exhaustion of this stem cell compartment in comparison to Ctip2(L2/L2) mice, which retained quiescent follicle stem cells. CTIP2 modulates expression of genes encoding EGFR and NOTCH1 during formation of hair follicles, and those encoding NFATC1 and LHX2 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 hair follicle morphogenesis and hair cycling.