OVOL2 Maintains the Transcriptional Program of Human Corneal Epithelium by Suppressing Epithelial-to-Mesenchymal Transition

In development, embryonic ectoderm differentiates into neuroectoderm and surface ectoderm using poorly understood mechanisms. Here, we show that the transcription factor OVOL2 maintains the transcriptional program of human corneal epithelium cells (CECs), a derivative of the surface ectoderm, and that OVOL2 may regulate the differential transcriptional programs of the two lineages. A functional screen identified OVOL2 as a repressor of mesenchymal genes to maintain CECs. Transduction of OVOL2 with several other transcription factors induced the transcriptional program of CECs in fibroblasts. Moreover, neuroectoderm derivatives were found to express mesenchymal genes, and OVOL2 alone could induce the transcriptional program of CECs in neural progenitors by repressing these genes while activating epithelial genes. Our data suggest that the difference between the transcriptional programs of some neuroectoderm- and surface ectoderm-derivative cells may be regulated in part by a reciprocally repressive mechanism between epithelial and mesenchymal genes, as seen in epithelial-to-mesenchymal transition. [Display omitted] •Identification of a transcription factor that can functionally maintain human CECs•OVOL2 can activate CEC-specific genes in heterologous cell types•OVOL2 represses mesenchymal genes in CECs•EMT may regulate transcriptional programs of surface and neuroectoderm Kitazawa et al. show that the transcription factor OVOL2 maintains the transcriptional program of corneal epithelial cells by repressing mesenchymal genes and EMT. This may allow OVOL2 to regulate the differential transcriptional programs of the surface ectoderm and the neuroectoderm.