biostudies-literatureUnknownTang QNational Center for Advancing Translational SciencesNCATS NIH HHSNIDCR NIH HHSNational Institute of Dental and Craniofacial ResearchTooth enamel, the hardest vertebrate tissue, is crucial for mastication and dental protection. Its formation depends on the enamel organ (EO), a specialized epithelial structure derived from oral epithelium. How uniform oral epithelium differentiates into diverse EO cell types remains unclear. While <i>p63</i>, an ectodermal development master regulator, is essential for dental placode formation, its specific roles in EO development have been obscured by early arrest in p63 knockout mice. Using single-cell RNA sequencing from mouse incisors, we show <i>p63</i> expression across all EO cell types with both shared and distinct functions. Through trajectory reconstruction, we identify <i>p63</i>'s role in regulating both amelogenic (AmG) and non-AmG lineage commitment during EO development. CbioRxiv : the preprint server for biology2025.02.11.637463https://www.ebi.ac.uk/biostudies/studies/S-EPMC11844444biostudies-literaturep63 co-opts the skin Krt8-to-Krt5 transition for enamel organ development.PMC11844444T32DE023526KL2TR001413R03 DE030985UL1TR001412T32 DE023526R01 DE033085UL1 TR001412R03DE030985R01DE033085KL2 TR001413Kwon HECai CTang QJung HLee JMLi Lfalsep63 co-opts the skin Krt8-to-Krt5 transition for enamel organ development.Tooth enamel, the hardest vertebrate tissue, is crucial for mastication and dental protection. Its formation depends on the enamel organ (EO), a specialized epithelial structure derived from oral epithelium. How uniform oral epithelium differentiates into diverse EO cell types remains unclear. While <i>p63</i>, an ectodermal development master regulator, is essential for dental placode formation, its specific roles in EO development have been obscured by early arrest in p63 knockout mice. Using single-cell RNA sequencing from mouse incisors, we show <i>p63</i> expression across all EO cell types with both shared and distinct functions. Through trajectory reconstruction, we identify <i>p63</i>'s role in regulating both amelogenic (AmG) and non-AmG lineage commitment during EO development. C2025-01-01T00:00:00Z2025 Apr2026-07-03T03:23:03.69Z2025-04-04T01:12:42.703ZS-EPMC118444443999038610.1101/2025.02.11.637463