title: Inhibition of Notch Signaling During Mouse Incisor Renewal Leads to Enamel Defects.
abstract: 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.
authors.affiliation: Department of Orofacial Sciences and Program in Craniofacial Biology, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Jheon
authors.affiliation: Department of Orofacial Sciences and Program in Craniofacial Biology, University of California San Francisco, San Francisco, CA, USA.|Department of Anthropology and Human Genetics, Charles University, Prague, Czech Republic.
authors.forename: Michaela
authors.initials: M
authors.lastname: Prochazkova
authors.affiliation: Department of Orofacial Sciences and Program in Craniofacial Biology, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Meng
authors.affiliation: Department of Orofacial Sciences and Program in Craniofacial Biology, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Timothy
authors.initials: T
authors.lastname: Wen
authors.affiliation: Department of Orofacial Sciences and Program in Craniofacial Biology, University of California San Francisco, San Francisco, CA, USA.|Seoul National University, Seoul, South Korea.
authors.forename: Young-Jun
authors.initials: YJ
authors.lastname: Lim
authors.affiliation: Department of Orofacial Sciences and Program in Craniofacial Biology, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Adrien
authors.initials: A
authors.lastname: Naveau
authors.affiliation: Department of Orofacial Sciences and Program in Craniofacial Biology, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Ruben
authors.initials: R
authors.lastname: Espinoza
authors.affiliation: Department of Pediatrics (Craniofacial Medicine), University of Washington, & Center for Developmental Biology and Regenerative Medicine, Seattle Children's Research Institute, Seattle, WA, USA.
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Cox
authors.affiliation: Institute of Biomaterials and Biomedical Engineering, Department of Materials Science and Engineering, and Faculty of Dentistry, University of Toronto, Toronto, Canada.
authors.forename: Eli D
authors.initials: ED
authors.lastname: Sone
authors.affiliation: Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Canada.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Ganss
authors.affiliation: Department of Discovery Oncology, Genentech, San Francisco, CA, USA.
authors.forename: Christian W
authors.initials: CW
authors.lastname: Siebel
authors.affiliation: 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.
authors.forename: Ophir D
authors.initials: OD
authors.lastname: Klein
mesh_terms: D000565:Ameloblasts / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D003743:Dental Enamel / Q000378:metabolism* / Q000473:pathology; D003896:Desmosomes / Q000378:metabolism / Q000473:pathology; D007180:Incisor / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D051880:Receptors, Notch; D015398:Signal Transduction; D014076:Tooth Diseases
chemical_list: D051880:Receptors, Notch
keywords: AMELOBLAST; AMELOGENESIS; JAG; NOTCH; STRATUM INTERMEDIUM; TOOTH DEVELOPMENT