Dermal Blimp1 Acts Downstream of Epidermal TGFβ and Wnt/β-Catenin to Regulate Hair Follicle Formation and Growth

• DOI: 10.1016/j.jid.2017.06.015
• Publication Date: 2017-06-28T13:45:16Z
• Authors: Stephanie B. Tele...; Emanuel Rognoni; Inês Sequeira; Angela Oliveira P...; Beate M. Lichtenb...; Oliver J. Culley; Priyalakshmi Visw...; Ryan R. Driskell; Fiona M. Watt
• Keywords: dermal fibroblasts; Male; 0301 basic medicine; 570; Blimp1; 610; Down-Regulation; wound healing; Cell Communication; Article; TGFβ; Mice; 03 medical and health sciences; Animals; RNA, Messenger; Cells, Cultured; hair follicles; Cell Proliferation; Wnt/β-catenin; Biopsy, Needle; Cell Differentiation; Immunohistochemistry; Mice, Inbred C57BL; Disease Models, Animal; Epidermal Cells; Gene Expression Regulation; Prdm1; Mice, Inbred CBA; Female; Positive Regulatory Domain I-Binding Factor 1; Epidermis; Hair Follicle

B-lymphocyte-induced maturation protein 1 (Blimp1) is a transcriptional repressor that regulates cell growth and differentiation in multiple tissues, including skin. Although in the epidermis Blimp1 is important for keratinocyte and sebocyte differentiation, its role in dermal fibroblasts is unclear. Here we show that Blimp1 is dynamically regulated in dermal papilla cells during hair follicle (HF) morphogenesis and the postnatal hair cycle, preceding dermal Wnt/β-catenin activation. Blimp1 ablation in E12.5 mouse dermal fibroblasts delayed HF morphogenesis and growth and prevented new HF formation after wounding. By combining targeted quantitative PCR screens with bioinformatic analysis and experimental validation we demonstrated that Blimp1 is both a target and a mediator of key dermal papilla inductive signaling pathways including transforming growth factor-β and Wnt/β-catenin. Epidermal overexpression of stabilized β-catenin was able to override the HF defects in Blimp1 mutant mice, underlining the close reciprocal relationship between the dermal papilla and adjacent HF epithelial cells. Overall, our study reveals the functional role of Blimp1 in promoting the dermal papilla inductive signaling cascade that initiates HF growth.