Requirement of Wnt Modulator R-Spondin3 in Craniofacial Morphogenesis and Dental Development
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CitationAlhazmi, Nora. 2020. Requirement of Wnt Modulator R-Spondin3 in Craniofacial Morphogenesis and Dental Development. Doctoral dissertation, Harvard School of Dental Medicine.
AbstractWnt signaling plays a critical role in craniofacial, tooth and bone development. Rspo3 is a key regulator of Wnt signaling; however, its function in craniofacial development and skeletogenesis is unknown. We show that Rspo3 is expressed in perichondrial cells and osteoprogenitors in the developing embryonic palate and Meckel’s cartilage in both zebrafish and mouse. In zebrafish, where tooth replacement is cyclic and occurs throughout the life of the animal, rspo3 appears to be broadly expressed in the pulp, odontoblasts and epithelial crypts, and preferentially labels emerging teeth. Consistent with results obtained in the zebrafish, Rspo3 is expressed in odontoblasts, pulp, ameloblasts and alveolar bone in the mouse. Using the zebrafish model, we show that rspo3 disruption affects canonical Wnt signaling during embryogenesis. While mouse Rspo3 global knockout is embryonic lethal, zebrafish rspo3-/- mutants are viable and show defects in the development of forming embryonic palate and in Meckel’s cartilage morphology. Adult rspo3-/- mutant zebrafish exhibit decreased body length, hypodontia and abnormal dental morphology. Disruption of rspo3 during zebrafish development resulted in poor ossification and dysmorphology of the adult zebrafish craniofacial skeleton and teeth. This study highlights the key functions of Rspo3 in osteogenesis and morphogenesis of dentocranial structures.
Citable link to this pagehttps://nrs.harvard.edu/URN-3:HUL.INSTREPOS:37365591