Figure 2.

Schematic diagram depicting the main events during amelogenesis. (A) Pre-secretory stage: Ameloblasts (blue) differentiate from the cells of the inner enamel epithelium (IEE), in response to reciprocal signaling between the IEE and the dental papilla. The basal lamina between the IEE and dental papilla breaks down so that the cells are in contact with the pre-dentine. The ameloblasts elongate and their nuclei shift to the proximal side of the cell, nearest the stratum intermedium (SI), resulting in reversal of the ameloblasts' polarity. At the distal end, closest to the pre-dentine, the Golgi apparatus and rough endoplasmic reticulum increase in size to increase the capacity for protein production, post translational modification and secretion. The non-dividing cell becomes further polarized as it forms a distal extension that will go on to form the Tomes' process (TP). Each ameloblast develops and maintains anchoring junctions to hold the ameloblast layer in alignment and to control what passes between them. (B–D) Secretory stage: During the secretory stage, a proteinaceous extracellular matrix is secreted from the ameloblast TP, as the ameloblast layer retreats from the dentine layer. To achieve this, ameloblasts produce large amounts of membrane bound, secretory granules containing enamel matrix proteins (EMPs). EMPs are constitutively secreted via exocytosis into the extracellular space at the distal end of the cell, on to the newly formed dentine. (B) Mineral immediately forms in this initial enamel matrix and forms a close association with the dentine mineral. This will form the aprismatic enamel. (C) The ameloblasts begin to move away from the dentine and further develop their TP at the distal end. EMPs are secreted from two aspects of the ameloblasts to produce enamel matrix that will go on to form the prismatic and interprismatic enamel. (D) As secretion progresses the TP lengthens and thins. The portion secreting the prismatic enamel is reduced before secretion ceases, therefore the final enamel formed will be aprismatic. (E) Transition stage: The transition stage is characterized by reduced EMP secretion and internal reorganization of the ameloblasts. Ameloblasts shorten to around half their original height and reduce in volume. Their nuclei become more central and the ER is reduced in size. The TP is completely lost and an atypical basal lamina is formed against the enamel matrix. Ameloblasts adhere to the enamel matrix via hemidesmosomes. The cells of the SI, stellate reticulum and the outer enamel epithelium form the papillary layer (PL). Capillaries invaginate into this layer and overlay the ameloblasts. The cells of the PL may assist ameloblasts in the maturation stage by participating in ion transport and removal of enamel protein products and water from the developing enamel. The ameloblast population reduces by around 25% at this stage through apoptosis. (F) and (G) Maturation stage: During the maturation stage the partially mineralized enamel matrix becomes fully mineralized by the breakdown and removal of residual EMPs, and the growth in width and thickness of enamel crystallites. These processes are achieved through repeated cyclical processes. The ameloblasts act as a gated barrier for the movement of ions and degraded proteins between the SI and the developing enamel and vice versa. To achieve this, the ameloblast membrane facing the enamel matrix modulates between ruffle ended (F) and smooth ended (G) morphologies. This is achieved in coordinated groups of ameloblasts across the developing enamel. Ruffle ended ameloblasts (RA) form membrane invaginations and tight junctions at the apical end, near the enamel surface, whereas smooth ended ameloblasts (SA) are more leaky. Enamel crystal growth generates large amounts of protons but it has also been shown that protons are pumped into the enamel by RA. Both RA and SA release bicarbonate ions into the enamel that act as a buffer to increase pH. A mildy acidic pH is found in enamel at RA regions and a more neutral pH in SA regions. During maturation around 25% of ameloblasts apoptose. (H) Post-maturation stage: The ameloblasts and other cells of the enamel organ, form the reduced enamel epithelium, which eventually contributes to the junctional epithelium of mature teeth. However, many of the ameloblasts apoptose before the formation of the junction epithelium is completed.