R-Spondin 3 Regulates Mammalian Dental and Craniofacial Development.

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 in mice led to supernumerary lower molars, while teeth forming at the normal positions showed no significant anomalies. Because multiple genes are expressed in the orofacial region, it is possible that the relatively mild phenotype of mutants is due to functional compensation by other RSPO proteins. We found that inactivating in the craniofacial mesenchyme caused the loss of lower incisors, which did not progress beyond the bud stage. A simultaneous deletion of and caused severe disruption of craniofacial development from early stages, which was accompanied with impaired development of all teeth. Together, these results indicate that is an important regulator of mammalian dental and craniofacial development.