Human tooth development

Abstract: Members of the decapentaplegic-Vg-related (DVR) gene family are diffusible signaling molecules regulating inductive tissue interactions during vertebrate development. Expression of DVR/bone morphogenetic protein (BMP) 2, 4, and 6 was studied in human fetal teeth. Sequential morphogenetic stage-specific studies of DVR/BMP 2 and 4 mRNA expression by in situ hybridization revealed transcripts for DVR/BMP 4 during compaction of the dental mesenchyme. In contrast, DVR/BMP 2 mRNA appeared later during tooth development and was located in differentiated cells (odontoblasts). These results were confirmed by reverse-transcription polymerase chain reaction (RT-PCR), which detected DVR/BMP 2 and 4 mRNA in human tooth-germ samples. DVR/BMP 6 protein was distributed in the early dental epithelium and, later, in pre-odontoblasts and odontoblasts, where it remained during dentin formation. These results suggest that DVR/BMP 4 is involved in the early tooth morphogenesis. DVR/BMP 6 may, in particular, be implicated in epithelial-mesenchymal interactions controlling cytodifferentiation. DVR/BMP 2 and 6 may also be involved in odontoblast secretory function. The results suggest that members of the DVR gene family may play regulatory roles during human tooth development.

Abstract: The upper lateral incisor in humans is often affected by dental anomalies that might be explained developmentally. To address this question, we investigated the origin of the deciduous upper lateral incisor (i2) in normal human embryos at prenatal weeks 6-8. We used serial frontal histological sections and computer-aided 3D reconstructions. At embryonic days 40-42, two thickenings of the dental epithelia in an "end-to-end" orientation were separated by a groove at the former fusion site of the medial nasal and maxillary processes. Later, these dental epithelia fused, forming a continuous dental lamina. At the fusion site, i2 started to develop. The fusion line was detectable on the i2 germ until the 8th prenatal week. The composite origin of the i2 may be associated with its developmental vulnerability. From a clinical aspect, a supernumerary i2 might be a form of cleft caused by a non-fusion of the dental epithelia.

Abstract: In this review, we discuss the central role of fibroblast growth factor (FGF) signaling in mammalian tooth development. The FGF family consists of 22 members, most of which bind to four different receptor tyrosine kinases, which in turn signal through a cascade of intracellular proteins. This signaling regulates a number of cellular processes, including proliferation, differentiation, cell adhesion and cell mobility. FGF signaling first becomes important in the presumptive dental epithelium at the initiation stage of tooth development, and subsequently, it controls the invagination of the dental epithelium into the underlying mesenchyme. Later, FGFs are critical in tooth shape formation and differentiation of ameloblasts and odontoblasts, as well as in the development and homeostasis of the stem cell niche that fuels the continuously growing mouse incisor. In addition, FGF signaling is critical in human teeth, as mutations in genes encoding FGF ligands or receptors result in several congenital syndromes characterized by alterations in tooth number, morphology or enamel structure. The parallel roles of FGF signaling in mouse and human tooth development demonstrate the conserved importance of FGF signaling in mammalian odontogenesis.

Abstract: Cadherins are calcium-dependent cell adhesion molecules involved in the regulation of various biological processes such as cell recognition, intercellular communication, cell fate, cell polarity, boundary formation, and morphogenesis. Although previous studies have shown E-cadherin expression during rodent or human odontogenesis, there is no equivalent study available on N-cadherin expression in dental tissues. Here we examined and compared the expression patterns of E- and N-cadherins in both embryonic and adult (healthy, injured, carious) human teeth. Both proteins were expressed in the developing teeth during the cap and bell stages. E-cadherin expression in dental epithelium followed an apical-coronal gradient that was opposite to that observed for N-cadherin. E-cadherin was distributed in proliferating cells of the inner and outer enamel epithelia but not in differentiated cells such as ameloblasts, whereas N-cadherin expression was up-regulated in differentiated epithelial cells. By contrast to E-cadherin, N-cadherin was also expressed in mesenchymal cells that differentiate into odontoblasts and produce the hard tissue matrix of dentin. Although N-cadherin was not detected in permanent intact teeth, it was re-expressed during dentin repair processes in odontoblasts surrounding carious or traumatic sites. Similarly, N-cadherin re-expression was seen in vitro, in cultured primary pulp cells that differentiate into odontoblast-like cells. Taken together these results suggest that E- and N-cadherins may play a role during human tooth development and, moreover, indicate that N-cadherin is important for odontoblast function in normal development and under pathological conditions.