NF-κB Participates in Mouse Hair Cycle Control and Plays Distinct Roles in the Various Pelage Hair Follicle Types

The transcription factor NF-κB controls key features of hair follicle (HF) development, but the role of NF-κB in adult HF cycle regulation remains obscure. Using NF-κB reporter mouse models, strong NF-κB activity was detected in the secondary hair germ of late telogen and early anagen HFs, suggesting a potential role for NF-κB in HF stem/progenitor cell activation during anagen induction. At mid-anagen, NF-κB activity was observed in the inner root sheath and unilaterally clustered in the HF matrix, which indicates that NF-κB activity is also involved in hair fiber morphogenesis during HF cycling. A mouse model with inducible NF-κB suppression in the epithelium revealed pelage hair-type−dependent functions of NF-κB in cycling HFs. NF-κB participates in telogen−anagen transition in awl and zigzag HFs, and is required for zigzag hair bending and guard HF cycling. Interestingly, zigzag hair shaft bending depends on noncanonical NF-κB signaling, which previously has only been associated with lymphoid cell biology. Furthermore, loss of guard HF cycling suggests that in this particular hair type, NF-κB is indispensable for stem cell activation, maintenance, and/or growth.