Dicer is required for maintenance of hair follicle stem cells in adult skin

Abstract

Multiple miRNAs are expressed in developing and postnatal skin and hair follicles, and constitutive deletion of the miRNA processing enzyme Dicer in embryonic mouse skin causes failure of hair follicle morphogenesis and subsequent follicular degradation. To determine whether Dicer and miRNA functions are required in established hair follicles and epidermis in the adult mouse we generated Krt5-rtTA tetO-Cre Dicerfl/fl mice in which the Dicer gene can be inducibly deleted in the basal epidermis and hair follicle outer root sheath, including hair follicle stem cells, by dosage with oral doxycycline. Inducible Dicer deletion starting at postnatal day (P) 20, when hair follicles are just entering the first postnatal growth cycle, resulted in loss of external hair starting within 10days of doxycycline treatment. Induction of mutation during the resting stage of the hair follicle growth cycle did not immediately result in histological abnormalities or loss of hair. However, expression of the hair follicle bulge stem cell markers K15 and CD34 was lost soon after induction. Subsequent hair plucking stimulated a new cycle of hair follicle growth in control littermate, but not induced Dicer mutant skin. These results demonstrate a requirement for Dicer in maintaining the ability of adult hair follicles to grow and regenerate, and indicate that Dicer is required for maintenance of hair follicle epithelial stem cells.