Molecular genetics of ameloblast cell lineage

Abstract

Late tooth morphogenesis is characterized by a series of events that determine crown morphogenesis and the histodifferentiation of epithelial cells into enamel-secreting ameloblasts and of mesenchymal cells into dentin-secreting odontoblasts. Functional ameloblasts are tall, columnar, polarized cells that synthesize and secrete a number of enamel-specific proteins. After depositing the full thickness of enamel matrix, ameloblasts shrink in size and regulate enamel maturation. Amelogenesis imperfecta (AI) is a heterogeneous group of inherited defects in enamel formation. Clinically, AI presents as a spectrum of enamel malformations that are categorized as hypoplastic, hypocalcified, or hypomaturation types, based upon the thickness and hardness of the enamel. The different types of AI are inherited, either as X-linked, autosomal-dominant, or autosomal-recessive traits. Recently, several gene mutations have been identified to cause the subtypes of AI. How these genes, however, coordinate their function to control amelogenesis is not understood. In this review, we discuss the role of genes that play definitive role on the determination of ameloblast cell fate and life cycle based on studies in transgenic animals.

Figure 1. Ameloblast life cycle

(A) H&E stained wild type incisor teeth showing the life cycle of ameloblasts. (i): morphogenetic stage; (ii)&(iii): initial secretory (no Tomes' process) and secretory ameloblasts (with Tomes' processes that secrete enamel) and (iv): maturation stages. Abbreviations: a: ameloblasts; o: odontoblasts; e: enamel matrix; d: dentin. (B): TEM of ameloblasts at the secretory stage of their life cycle. The ameloblasts at this stage are characterized by an extensive rER, a Golgi complex located in the center of the cytoplasm, condensed and packaged into membrane-bound secretory granules that migrate to the distal part of the cell. After the first deposition of enamel matrix (structure-less enamel layer) the ameloblasts are migrating proximally and processes, known as Tomes' processes, are developed. The cytoplasm of the ameloblast continues into the process but distinct border between them is marked by the presence of the distal terminal web and junctional complex. Abbreviations: M: mitochondria; nu: nucleus; rER: secretory ameloblasts; sg: secretory granules; Tp: Tomes' process; er: enamel rod; e: enamel; TW: terminal web; d: dentin.

Figure 2. Msx2 mutant ameloblasts exhibit defective cell-cell adhesion

(A) Wild type ameloblasts at the secretory stage are elongated, highly polarized cells, tightly connected to each other. (B) Msx2 mutant ameloblasts are polarized and enamel matrix is formed. In contrast to wild type, Msx2 mutant ameloblasts exhibit a marked absence of cell-cell adhesive junctions (see arrows between adjacent ameloblasts). Abbreviations: nu: nucleus; rER: ribosomal endoplasmic reticulum; si: stratum intermedium (Modified from Bei et al., 2004).