Cutaneous Retinoic Acid Levels Determine Hair Follicle Development And Downgrowth

The study demonstrated that specific levels of retinoic acid (RA), regulated by the enzyme Cyp26b1, are crucial for hair follicle morphogenesis. Mice lacking Cyp26b1 (Cyp26b1−/−) exhibited excessive RA and their hair follicle growth was arrested at the hair germ stage. This abnormal development could be rescued by grafting the mutant skin onto immunodeficient mice, which normalized RA levels and allowed hair follicle development to resume. Additionally, a conditional deficiency of Cyp26b1 in the dermis (En1Cre;Cyp26b1f/−) led to reduced hair follicle density and affected hair type, suggesting that RA levels also influence hair bending regulators. The study also identified that RA affects the Wnt-catenin pathway and transcription factors from the Runx, Fox, and Sox families, which are involved in hair follicle downgrowth and bending. These findings underscore the importance of proper RA distribution for hair follicle morphogenesis, development, and differentiation.