Enamel (E) is missing in mice that do not make ameloblastin (right).
Enamel is made by ameloblasts, which differentiate from oral epithelial precursors. Most of the enamel matrix consists of amelogenin, but ameloblasts also secrete several other matrix proteins, including ameloblastin. Fukumoto et al. show that ameloblastin is a cellular adhesive needed to maintain ameloblast differentiation.
In mice lacking ameloblastin, ameloblasts formed as usual at early stages. But they later detached from their matrix at a time when the surface is normally replaced with enamel matrix proteins. The detached ameloblasts lost their cell polarity and returned to a less differentiated, proliferative state. The epithelium-derived oral tumors that were found in the adult mutant mice probably formed from these proliferative cells.
The cells detached because ameloblastin was not there to substitute for the basement membrane that was degraded during enamel secretion. Ameloblast precursors used the basement membrane as adhesive, but the differentiated ameloblasts bound only to ameloblastin. If the authors can identify the cell receptor for ameloblastin, they may be able to determine the signaling pathways that maintain differentiation in the matrix-adhered cells. 
