A new research study published in the November issue of Developmental Cell identifies a molecular mechanism that controls the precise patterning of enamel formation on incisor teeth. Mouse incisors are covered with enamel on the side closest to the lip while the side facing the tongue remains enamel-free. This irregular distribution of enamel helps to keep the cutting edges of the incisors very sharp. While it is well established that cells called ameloblasts secrete enamel, the molecular signals regulating asymmetric ameloblast differentiation from the underlying dental epithelium are not well understood.
Dr. Irma Thesleff and colleagues from the Institute of Biotechnology at the University of Helsinki examined the contribution of a gene called follistatin to the process of tooth development. Follistatin plays a critical role in the patterning of several organs during embryogenesis. The researchers found that follistatin was expressed at low levels in active ameloblasts and at much higher levels in the dental epithelial cells lining the enamel-free surface of the incisors. Mice engineered to lack follistatin had functional ameloblasts on the normally enamel-free surface adjacent to the tongue. Further investigation revealed that follistatin prevents enamel formation by inhibiting BMP signaling molecules that are potent stimulators of ameloblast differentiation.
The researchers conclude that asymmetric expression of follistatin accounts for the distinct patterning of enamel formation in mouse incisors and that follistatin expression is required for formation of enamel-free tooth regions. While the mechanism that dampens follistatin expression in unknown, it is clear that the lack of follistatin allows BMP signals to stimulate ameloblast differentiation on the labial side of the incisor.
Xiu-Ping Wang, Marika Suomalainen, Carolina J. Jorgez, Martin M. Matzuk, Sabine Werner, and Irma Thesleff: "Follistatin Regulates Enamel Patterning in Mouse Incisors by Asymmetrically Inhibiting BMP Signaling and Ameloblast Differentiation"
Publishing in Developmental Cell, Volume 7, Number 5, November 2004, pages 719–730.