Tooth enamel, the hardest tissue in vertebrates, is crucial for mastication and dental protection. Its formation depends on the enamel organ (EO), a specialized epithelial structure derived from oral epithelium. A fundamental question persists: how does uniform oral epithelium differentiate into diverse EO cell types? While p63, a master regulator of ectodermal development, coordinates multiple signaling pathways essential for dental placode formation, its specific roles in EO development remain unclear due to the early developmental arrest in