WNT molecules are the regulators of various biological functions, including body axis formation, organ development, and cell proliferation and differentiation. WNTs have been extensively studied as causative genes for an array of diseases. WNT10A and WNT10B, which are considered to be genes of the same origin, have been identified as causative genes for tooth deficiency in humans. However, the disrupted mutant of each gene does not show a decrease in teeth number. A negative feedback loop, interacting with several ligands based on a reaction-diffusion mechanism, was proposed to be important for the spatial patterning of tooth formation, and WNT ligands have been considered to play a pivotal role in controlling tooth patterning from mutant phenotypes of LDL receptor-related proteins (LRPs) and WNT co-receptors. The Wnt10a and Wnt10b double-mutants demonstrated severe root or enamel hypoplasia. In Wnt10a-/- and Wnt10a+/-;Wnt10b-/- mice, changes in the feedback loop may collapse the modulation of fusion or split a sequence of tooth formation. However, in the double-knockout mutant, a decrease in the number of teeth was observed, including the upper incisor or third molar in both jaws. These findings suggest that there may be a functional redundancy between Wnt10a and Wnt10b and that the interaction between the two genes functions in conjunction with other ligands to control the spatial patterning and development of teeth.
Keywords: WNT10A; WNT10B; double mutations; functional redundancy; oligodontia; tooth number.