Tooth developmental biology: disruptions to enamel-matrix assembly and its impact on biomineralization

Dental enamel is a composite bioceramic material that is the hardest tissue in the vertebrate body, containing long, thin crystallites of substituted hydroxyapatite (HAP). Over a lifetime of an organism, enamel functions under repeated and immense loads, generally without catastrophic failure. Enamel is a product of ectoderm-derived cells called ameloblasts. Recent investigations on the formation of enamel using cell and molecular approaches are now being coupled to biomechanical investigations at the nanoscale and mesoscale levels. For amelogenin, the principal structural protein for forming enamel, we have identified two domains that are required for its proper self-assembly into supramolecular structures referred to as nanospheres. Nanospheres are believed to control HAP crystal habit. Other structural proteins of the enamel matrix include ameloblastin and enamelin, but little is known about their biological importance. Transgenic animals have been prepared to investigate the effect of overexpression of wild-type or mutated enamel proteins on the developing enamel matrix. Amelogenin transgenes were engineered to contain deletions to either of the two self-assembly domains and these alterations produced significant defects in the enamel. Additional transgenic animal lines have been prepared and studied and each gives additional insights into the mechanisms for enamel biofabrication. This study summarizes the observed enamel phenotypes of recently derived transgenic animals. These data are being used to help define the role of each of the enamel structural proteins in enamel and study how each of these proteins impact on enamel biomineralization.