Synergistic roles of amelogenin and ameloblastin

Amelogenin and ameloblastin, the major enamel matrix proteins, are important for enamel mineralization. To identify their synergistic roles in enamel development, we generated Amel X^-/-/Ambn^-/- mice. These mice showed additional enamel defects in comparison with Amel X ^-/- or Ambn^-/- mice. In 7-day-old Amel X ^-/-/Ambn^-/- mice, not only was the ameloblast layer irregular and detached from the enamel surface, as in Ambn^-/-, but also, the enamel width was significantly reduced in the double-null mice as compared with Amel X^-/- or Ambn^-/- mice. Proteomic analysis of the double-null teeth revealed increased levels of RhoGDI (Arhgdia), a Rho-family-specific guanine nucleotide dissociation inhibitor, which is involved in important cellular processes, such as cell attachment. Both Amel X^-/-/Ambn^-/- mice and Ambn^-/- mice displayed positive staining with RhoGDI antibody in the irregularly shaped ameloblasts detached from the matrix. Ameloblastin-regulated expression of RhoGDI suggests that Rho-mediated signaling pathway might play a role in enamel formation.