biostudies-literatureMitsiadis TADeutsche ForschungsgemeinschaftUniversität Zürich105154https://www.ebi.ac.uk/biostudies/studies/S-EPMC9526176biostudies-literatureUnknown25(10)The disintegrin and metalloproteinase Adam10 is a membrane-bound sheddase that regulates Notch signaling and ensures epidermal integrity. To address the function of Adam10 in the continuously growing incisors, we used Keratin14 Cre/+;Adam10 fl/fl transgenic mice, in which Adam10 is conditionally deleted in the dental epithelium. Keratin14 Cre/+;Adam10 fl/fl mice exhibited severe abnormalities, including defective enamel formation reminiscent of human enamel pathologies. Histological analyses of mutant incisors revealed absence of stratum intermedium, and severe disorganization of enamel-secreting ameloblasts. In situ hybridization and immunostaining analyses in the Keratin14 Cre/+;Adam10 <iScienceAdam10-dependent Notch signaling establishes dental epithelial cell boundaries required for enamel formation.PMC9526176SFB877-A3Jimenez-Rojo LPagella PMitsiadis TAWeber SSaftig PBalic AfalseAdam10-dependent Notch signaling establishes dental epithelial cell boundaries required for enamel formation.The disintegrin and metalloproteinase Adam10 is a membrane-bound sheddase that regulates Notch signaling and ensures epidermal integrity. To address the function of Adam10 in the continuously growing incisors, we used Keratin14 Cre/+;Adam10 fl/fl transgenic mice, in which Adam10 is conditionally deleted in the dental epithelium. Keratin14 Cre/+;Adam10 fl/fl mice exhibited severe abnormalities, including defective enamel formation reminiscent of human enamel pathologies. Histological analyses of mutant incisors revealed absence of stratum intermedium, and severe disorganization of enamel-secreting ameloblasts. In situ hybridization and immunostaining analyses in the Keratin14 Cre/+;Adam10 <2022-01-01T00:00:00Z2022 Oct2025-04-19T11:33:04.544Z2025-02-19T00:23:29.937ZS-EPMC95261763619304810.1016/j.isci.2022.105154