The continuously growing rodent incisor is an emerging model for the study of renewal of mineralized tissues by adult stem cells. Although the Bmp, Fgf, Shh, and Wnt pathways have been studied in this organ previously, relatively little is known about the role of Notch signaling during incisor renewal. Notch signaling components are expressed in enamel-forming ameloblasts and the underlying stratum intermedium (SI), which suggested distinct roles in incisor renewal and enamel mineralization. Here, we injected adult mice with inhibitory antibodies against several components of the Notch pathway. This blockade led to defects in the interaction between ameloblasts and the SI cells, which ultimately affected enamel formation. Furthermore, Notch signaling inhibition led to the downregulation of desmosome-specific proteins such as PERP and desmoplakin, consistent with the importance of desmosomes in the integrity of ameloblast-SI attachment and enamel formation. Together, our data demonstrate that Notch signaling is critical for proper enamel formation during incisor renewal, in part by regulating desmosome-specific components, and that the mouse incisor provides a model system to dissect Jag-Notch signaling mechanisms in the context of mineralized tissue renewal.

Department of Anthropology and Human Genetics Charles University Prague Czech Republic

Department of Discovery Oncology Genentech San Francisco CA USA

Department of Orofacial Sciences and Program in Craniofacial Biology University of California San Francisco San Francisco CA USA

Department of Pediatrics and Institute for Human Genetics University of California San Francisco San Francisco CA USA

Department of Pediatrics University of Washington and Center for Developmental Biology and Regenerative Medicine Seattle Children's Research Institute Seattle WA USA

Institute of Biomaterials and Biomedical Engineering Department of Materials Science and Engineering and Faculty of Dentistry University of Toronto Toronto Canada

Matrix Dynamics Group Faculty of Dentistry University of Toronto Canada

Seoul National University Seoul South Korea

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Isl1 Controls Patterning and Mineralization of Enamel in the Continuously Renewing Mouse Incisor