SEBACEOUS GLANDS, NAILS AND THE CORNEA: INVESTIGATING THE ROLE OF SOX9 IN THE MAINTENANCE OF ECTODERMAL-DERIVED TISSUES AND APPENDAGES

Ectoderm-derived appendages and tissues offer an ideal model system for the study and manipulation of tissues. Located on the external surface of the body, these tissues are easily accessible and, in most cases, amenable to intravital imaging approaches to capture live cell behaviors. The transcription factor SOX9 is a known regulator of stem and progenitor cell fates in several adult tissues. In this study, we investigated the role of Sox9 as it pertained to homeostatic tissue maintenance of the hair follicle-associated sebaceous glands, the nail unit, and the corneal epithelium. To address the general role of Sox9 in the maintenance of ectodermal derived epithelial tissues, we generated conditional knockout models to delete Sox9 from these tissues in adult mice. In the sebaceous glands, we did not observe any obvious aberrant affects due to Sox9 loss. In the nail unit, or claw as it is referred to in mice, we discovered Sox9 uniquely marks the epithelial nail bed. Sox9 loss in the nail unit resulted in loss of the nail bed and expansion of the proliferative nail matrix, which resulted in unchecked growth and the development of thicker, unusually long claws. In the corneal epithelium, we identified a population of limbal stem cells marked by Sox9. Deleting Sox9 from the corneal epithelium resulted in the formation of keratinized, hyperplastic, skin-like growths at the central cornea. Together, the work in these tissues identified a role for Sox9 as being required for proper epithelial maintenance in the nail and cornea and provides novel insight into the versatile functions of Sox9 in regulating tissue homeostasis.