Adam10-dependent Notch signaling establishes dental epithelial cell boundaries required for enamel formation

Adam10-dependent Notch signaling establishes dental epithelial cell boundaries required for enamel formation

Blog Article

Summary: 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 Keratin14Cre/+;Adam10fl/fl transgenic mice, in which Adam10 is conditionally deleted in the dental epithelium.Keratin14Cre/+;Adam10fl/fl mice exhibited severe abnormalities, including defective enamel formation reminiscent of human enamel pathologies.Histological analyses of mutant incisors revealed absence of earthbath facial wipes stratum intermedium, and severe disorganization of enamel-secreting ameloblasts.

In situ hybridization and immunostaining analyses in the Keratin14Cre/+;Adam10fl/fl incisors ilootpaperie showed strong Notch1 downregulation in dental epithelium and ectopic distribution of enamel-specific molecules, including ameloblastin and amelogenin.Lineage tracing studies using Notch1CreERT2;R26mT/mG mice demonstrated that loss of the stratum intermedium cells was due to their fate switch toward the ameloblast lineage.Overall, our data reveal that in the continuously growing incisors the Adam10/Notch axis controls dental epithelial cell boundaries, cell fate switch and proper enamel formation.