Role of perlecan, a basement membrane-type heparan sulfate proteoglycan, in enamel organ morphogenesis

Perlecan is a multifunctional heparan sulfate proteoglycan that controls cell-signaling events by interacting with several growth factors, cytokines, and other signaling molecules. Perlecan was thought to be localized only in the basement membrane, but recently, intraepithelial localization of perlecan has been demonstrated in some pathophysiological situations. Therefore, perlecan is expected to modulate epithelial cell behavior. Our recent study demonstrated that perlecan accumulates in the stellate reticulum of the enamel organ of murine molar tooth germs in a stage-specific manner. To understand the function of perlecan in the enamel organ, we generated transgenic (Tg) mice that overexpressed perlecan in epithelial cells by using the keratin 5 promoter. Perlecan Tg molars had dull-ended crowns and outward-curved tooth roots, and their enamel was poorly crystallized. The constant overexpression of perlecan and the accompanying disorganized distribution of perlecan-related molecules in the enamel organ resulted in irregular tooth morphology. These results indicate that the time schedule of intraepithelial perlecan expression appears to be critically controlled during enamel organ development. In this brief review, we have described the dynamics of perlecan and its receptors and the timing of cleavage of heparan sulfate chains in odontogenesis, focusing on enamel organ development, and discussed the role of perlecan in enamel organ morphogenesis.