Abstract
Development of the teeth requires complex signaling interactions between the mesenchyme and the epithelium mediated by multiple pathways. For example, canonical WNT signaling is essential to many aspects of odontogenesis, and inhibiting this pathway blocks tooth development at an early stage. R-spondins (RSPOs) are secreted proteins, and they mostly augment WNT signaling. Although RSPOs have been shown to play important roles in the development of many organs, their role in tooth development is unclear. A previous study reported that mutating Rspo2 in mice led to supernumerary lower molars, while teeth forming at the normal positions showed no significant anomalies. Because multiple Rspo genes are expressed in the orofacial region, it is possible that the relatively mild phenotype of Rspo2 mutants is due to functional compensation by other RSPO proteins. We found that inactivating Rspo3 in the craniofacial mesenchyme caused the loss of lower incisors, which did not progress beyond the bud stage. A simultaneous deletion of Rspo2 and Rspo3 caused severe disruption of craniofacial development from early stages, which was accompanied with impaired development of all teeth. Together, these results indicate that Rspo3 is an important regulator of mammalian dental and craniofacial development.
Highlights
Tooth development in mammals is guided by reciprocal and dynamic interactions between the oral ectoderm and the underlying neural crest-derived mesenchyme
Signaling molecules involved in the process include fibroblast growth factors (FGF), bone morphogenetic proteins (BMP), winglesstype MMTV integration site family (WNT), and sonic hedgehog (SHH)
We examined mouse Rspo3 mutants and Rspo2; Rspo3 double mutants to demonstrate that Rspo3 is an important regulator of dental and craniofacial development
Summary
Tooth development in mammals is guided by reciprocal and dynamic interactions between the oral ectoderm and the underlying neural crest-derived mesenchyme. These interactions are mediated by many secreted signaling molecules and transcription factors, which are expressed in specific patterns. A recent paper showed that rspo and rspo regulated tooth numbers in fish [22], but they highlighted significant differences between fish and mice in Rspo expression patterns. We examined mouse Rspo mutants and Rspo; Rspo double mutants to demonstrate that Rspo is an important regulator of dental and craniofacial development
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