WNT7A and PAX6 define corneal epithelium homeostasis and pathogenesis

p63 and PAX6 act to specify limbal stem or progenitor cells (LSCs), and WNT7A controls corneal epithelium differentiation through PAX6; loss of WNT7A or PAX6 induces LSCs into epithelium, and transduction of PAX6 in skin epithelial stem cells converts them to LSC-like cells and transplantation in a rabbit corneal injury model can replenish corneal epithelial cells and repair damaged corneal surface. WNT7A and PAX6 signals in corneal pathogenesis The limbal stem cells (LSCs) in the basal limbal epithelium of the eye sustain corneal epithelial homeostasis and regeneration. Their loss due to injury or disease is one of the most common causes of blindness. Hong Ouyang et al . establish a method for culturing LSCs in a feeder-free medium. They identify the WNT7A–PAX6 signalling axis as a determinant of corneal lineage that has potential as a therapeutic target in corneal surface diseases. Transduction of PAX6 in skin epithelial stem cells converts them into LSC-like cells, and transplantation of the reprogrammed cells in a rabbit corneal injury model can repair damaged corneal surface. In a separate study in this issue of Nature , Bruce Ksander et al . identify a marker — the ABC transporter ABCB5 — that is functionally required for LSC maintenance, corneal development and repair, and can be used to identify LSCs in mouse and human eyes. LSC transplantation experiments suggest that ABCB5-expressing cells may have potential in the treatment of corneal disease, particularly corneal blindness due to LSC deficiency. The surface of the cornea consists of a unique type of non-keratinized epithelial cells arranged in an orderly fashion, and this is essential for vision by maintaining transparency for light transmission. Cornea epithelial cells (CECs) undergo continuous renewal from limbal stem or progenitor cells (LSCs) 1 , 2 , and deficiency in LSCs or corneal epithelium—which turns cornea into a non-transparent, keratinized skin-like epithelium—causes corneal surface disease that leads to blindness in millions of people worldwide 3 . How LSCs are maintained and differentiated into corneal epithelium in healthy individuals and which key molecular events are defective in patients have been largely unknown. Here we report establishment of an in vitro feeder-cell-free LSC expansion and three-dimensional corneal differentiation protocol in which we found that the transcription factors p63 (tumour protein 63) and PAX6 (paired box protein PAX6) act together to specify LSCs