Immunohistochemical localization of signal transduction pathways during amelogenesis: an initial exploration

This study was undertaken to map signal transduction pathway (STP) components uniquely associated with the four major receptor groups and their related STPs in association with the events involved in amelogenesis in the rat. Whole-head, freeze-dried sagittal sections were obtained at the level of the maxillary first molars and picked up on transparent adhesive tape. The sections were not decalcified or fixed, providing optimum conditions for immunohistochemical (IHC) localization. Antibodies to pathway components Gs alpha, Gi alpha, Gq alpha, Sos-1, Grb-2, p125Fak, Jak2, and Vav were localized. The respective patterns of localization indicate that the Gq alpha-linked, the receptor tyrosine kinase-initiated, and the integrin receptor-initiated pathways are involved in the proliferating pre-ameloblast cells. In the differentiating and differentiated ameloblasts, the Gs alpha-linked cAMP pathway is involved, apparently reading a factor(s) released by the dentin matrix. The Gq alpha-linked, the receptor tyrosine kinase-initiated, the integrin receptor-initiated, and the cytokine receptor-initiated pathways are also up-regulated in the proximal ends of the ameloblasts. These observations indicate that all four of the major receptor groups are involved in amelogenesis and that the role of classes of ligands not previously implicated in enamel formation must now be considered. It seems that the cells of the enamel organ respond to the appearance and disappearance of autocrine and paracrine growth factors, but they also up-regulate specific STPs to enable them to respond to circulating hormones and growth factors whose concentrations in the extracellular fluids remain relatively constant.