Dataset Information

Downregulation of FGF Signaling by Spry4 Overexpression Leads to Shape Impairment, Enamel Irregularities, and Delayed Signaling Center Formation in the Mouse Molar.

ABSTRACT: FGF signaling plays a critical role in tooth development, and mutations in modulators of this pathway produce a number of striking phenotypes. However, many aspects of the role of the FGF pathway in regulating the morphological features and the mineral quality of the dentition remain unknown. Here, we used transgenic mice overexpressing the FGF negative feedback regulator Sprouty4 under the epithelial keratin 14 promoter (K14-Spry4) to achieve downregulation of signaling in the epithelium. This led to highly penetrant defects affecting both cusp morphology and the enamel layer. We characterized the phenotype of erupted molars, identified a developmental delay in K14-Spry4 transgenic embryos, and linked this with changes in the tooth developmental sequence. These data further delineate the role of FGF signaling in the development of the dentition and implicate the pathway in the regulation of tooth mineralization. © 2019 The Authors. JBMR Plus is published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

SUBMITTER: Marangoni P

PROVIDER: S-EPMC6715786 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Downregulation of FGF Signaling by <i>Spry4</i> Overexpression Leads to Shape Impairment, Enamel Irregularities, and Delayed Signaling Center Formation in the Mouse Molar.

Marangoni Pauline P Charles Cyril C Ahn Youngwook Y Seidel Kerstin K Jheon Andrew A Ganss Bernhard B Krumlauf Robb R Viriot Laurent L Klein Ophir D OD

JBMR plus 20190731 8

FGF signaling plays a critical role in tooth development, and mutations in modulators of this pathway produce a number of striking phenotypes. However, many aspects of the role of the FGF pathway in regulating the morphological features and the mineral quality of the dentition remain unknown. Here, we used transgenic mice overexpressing the FGF negative feedback regulator Sprouty4 under the epithelial keratin 14 promoter (K14-<i>Spry4</i>) to achieve downregulation of signaling in the epithelium ...[more]

PMID: 31485553

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Project description:The form of two hard tissues of the mammalian tooth, dentine and enamel, is the result of a combination of the phylogenetic inheritance of dental traits and the adaptive selection of these traits during evolution. Recent decades have been significant in unveiling developmental processes controlling tooth morphogenesis, dental variation and the origination of dental novelties. The enamel-dentine junction constitutes a precursor for the morphology of the outer enamel surface through growth of the enamel cap which may go along with the addition of original features. The relative contribution of these two tooth components to morphological variation and their respective response to natural selection is a major issue in paleoanthropology. This study will determine how much enamel morphology relies on the form of the enamel-dentine junction. The outer occlusal enamel surface and the enamel-dentine junction surface of 76 primate second upper molars are represented by polygonal meshes and investigated using tridimensional topometrical analysis. Quantitative criteria (elevation, inclination, orientation, curvature and occlusal patch count) are introduced to show that the enamel-dentine junction significantly constrains the topographical properties of the outer enamel surface. Our results show a significant correlation for elevation, orientation, inclination, curvature and occlusal complexity between the outer enamel surface and the enamel dentine junction for all studied primate taxa with the exception of four modern humans for curvature (p<0.05). Moreover, we show that, for all selected topometrical parameters apart from occlusal patch count, the recorded correlations significantly decrease along with enamel thickening in our sample. While preserving tooth integrity by providing resistance to wear and fractures, the variation of enamel thickness may modify the curvature present at the occlusal enamel surface in relation to enamel-dentine junction, potentially modifying dental functionalities such as blunt versus sharp dental tools. In terms of natural selection, there is a balance between increasing tooth resistance and maintaining efficient dental tools. In this sense the enamel cap acts as a functional buffer for the molar occlusal pattern. In primates, results suggest a primary emergence of dental novelties on the enamel-dentine junction and a secondary transposition of these novelties with no or minor modifications of dental functionalities by the enamel cap. Whereas enamel crenations have been reported by previous studies, our analysis do not support the presence of enamel tubercles without dentine relief nuclei. As is, the enamel cap is, at most, a secondary source of morphological novelty.

Dataset Information

Downregulation of FGF Signaling by Spry4 Overexpression Leads to Shape Impairment, Enamel Irregularities, and Delayed Signaling Center Formation in the Mouse Molar.

Publications

Downregulation of FGF Signaling by <i>Spry4</i> Overexpression Leads to Shape Impairment, Enamel Irregularities, and Delayed Signaling Center Formation in the Mouse Molar.

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