Abstract
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 reciprocallyrepressive mechanism between epithelial and mesenchymal genes, as seen in epithelial-to-mesenchymal transition.
Highlights
RESULTSIn development, embryonic ectoderm differentiates into either neuroectoderm or a non-neural ectoderm, such as surface ectoderm (Ozair et al, 2013), which gives rise to epidermal tissues including the corneal epithelium
We found that neuroectoderm lineage cells expressed mesenchymal genes, of which repression by OVOL2 and activation of epithelial genes could induce the transcriptional program of corneal epithelium cells (CECs)
OVOL2 Repressed Mesenchymal Genes in CECs Because the functions of PAX6 and KLF4 in CEC maintenance have already been reported (Graw, 2003; Swamynathan et al, 2007), we examined how OVOL2 contributes to maintaining the transcriptional program of CECs using small interfering RNA in primary CECs
Summary
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.
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