DAPK1 orchestrates cell division and junction to control corneal epithelial development

Stratification of the corneal epithelium plays a vital role in protecting the eye from the external stimuli. However, the molecular mechanisms underlying this process are not fully understood. Herein, we show that death-associated protein kinase 1 (DAPK1) is markedly up-regulated during corneal epithelial development. Exploiting Dapk1 knockout mice, we show that depletion of DAPK1 results in corneal opacity and significant thickening of the corneal epithelium. Immunofluorescence staining using epithelial-specific markers reveals that DAPK1 deficiency causes the loss of corneal epithelial properties and the appearance of epidermal-like pathological changes. Further investigation shows that DAPK1 deficiency disrupts corneal epithelial stratification and impairs epithelial cell junctions due to the generation of excessive suprabasal cells through abnormal cell division. Therefore, this study demonstrates a critical role for DAPK1 in the control of corneal epithelial development, indicating DAPK1 as a potential therapeutic target for corneal diseases. • DAPK1 is significantly up-regulated during corneal epithelial stratification. • DAPK1 is essential for corneal epithelial development in the mouse model. • DAPK1 maintains the structural properties of the corneal epithelium. • DAPK1 regulates the division of basal cells in the corneal epithelium. • DAPK1 stabilizes cell junctions in the corneal epithelium.