TL;DR: The role of Shh is addressed in the developing tooth in mouse by using a conditional allele to remove Shh activity shortly after ingrowth of the dental epithelium and demonstrating that Shh regulates growth and determines the shape of the tooth.
Abstract: During mammalian tooth development, the oral ectoderm and mesenchyme coordinate their growth and differentiation to give rise to organs with precise shapes, sizes and functions. The initial ingrowth of the dental epithelium and its associated dental mesenchyme gives rise to the tooth bud. Next, the epithelial component folds to give the tooth its shape. Coincident with this process, adjacent epithelial and mesenchymal cells differentiate into enamel-secreting ameloblasts and dentin-secreting odontoblasts, respectively. Growth, morphogenesis and differentiation of the epithelium and mesenchyme are coordinated by secreted signaling proteins. Sonic hedgehog (Shh) encodes a signaling peptide which is present in the oral epithelium prior to invagination and in the tooth epithelium throughout its development. We have addressed the role of Shh in the developing tooth in mouse by using a conditional allele to remove Shh activity shortly after ingrowth of the dental epithelium. Reduction and then loss of Shh function results in a cap stage tooth rudiment in which the morphology is severely disrupted. The overall size of the tooth is reduced and both the lingual epithelial invagination and the dental cord are absent. However, the enamel knot, a putative organizer of crown formation, is present and expresses Fgf4, Wnt10b, Bmp2 and Lef1, as in the wild type. At birth, the size and the shape of the teeth are severely affected and the polarity and organization of the ameloblast and odontoblast layers is disrupted. However, both dentin- and enamel-specific markers are expressed and a large amount of tooth-specific extracellular matrix is produced. This observation was confirmed by grafting studies in which tooth rudiments were cultured for several days under kidney capsules. Under these conditions, both enamel and dentin were deposited even though the enamel and dentin layers remained disorganized. These studies demonstrate that Shh regulates growth and determines the shape of the tooth. However, Shh signaling is not essential for differentiation of ameloblasts or odontoblasts.
TL;DR: Key aspects of dental enamel formation are examined, from its developmental genesis to the ever-increasing wealth of data on the mechanisms mediating ionic transport, as well as the clinical outcomes resulting from abnormal ameloblast function.
Abstract: Dental enamel is the hardest and most mineralized tissue in extinct and extant vertebrate species and provides maximum durability that allows teeth to function as weapons and/or tools as well as for food processing. Enamel development and mineralization is an intricate process tightly regulated by cells of the enamel organ called ameloblasts. These heavily polarized cells form a monolayer around the developing enamel tissue and move as a single forming front in specified directions as they lay down a proteinaceous matrix that serves as a template for crystal growth. Ameloblasts maintain intercellular connections creating a semi-permeable barrier that at one end (basal/proximal) receives nutrients and ions from blood vessels, and at the opposite end (secretory/apical/distal) forms extracellular crystals within specified pH conditions. In this unique environment, ameloblasts orchestrate crystal growth via multiple cellular activities including modulating the transport of minerals and ions, pH regulation, proteolysis, and endocytosis. In many vertebrates, the bulk of the enamel tissue volume is first formed and subsequently mineralized by these same cells as they retransform their morphology and function. Cell death by apoptosis and regression are the fates of many ameloblasts following enamel maturation, and what cells remain of the enamel organ are shed during tooth eruption, or are incorporated into the tooth’s epithelial attachment to the oral gingiva. In this review, we examine key aspects of dental enamel formation, from its developmental genesis to the ever-increasing wealth of data on the mechanisms mediating ionic transport, as well as the clinical outcomes resulting from abnormal ameloblast function.
TL;DR: The basal lamina that is seen between the preameloblasts and the odontoblasts is removed before the deposition of mineral in the developing molar tooth of the rat, and correlation of electron and light micrographs clarifies the nature of “pre-enamel.”
TL;DR: These data are interpreted as an unequivocal demonstration of the inductive role of the dental mesenchyme and the nature of epithelio-mesenchymal interactions in the developing mouse integument.
Abstract: The response of embryonic mouse dental epithelium and mesoderm to tissues of ectopic origin was examined. Isolated molar or incisor mesoderm was confronted with epithelium isolated from the plantar surface of the embryonic mouse foot plate or from the snout. Harmoniously structured teeth were formed from the foot epithelium and incisor or molar mesoderm. These data are interpreted as an unequivocal demonstration of the inductive role of the dental mesenchyme. Teeth were absent in confrontations of dental mesenchyme and snout epithelium. The presence of hair follicles in these explants is described and discussed with reference to other integumental epithelio-mesenchymal interactions. Dental epithelium forms keratinizing surface-like epithelium and invading bands of epithelium in association with foot mesoderm; definitive structures are not formed. On the other hand, when incisor or molar epithelium is associated with snout mesoderm, hair follicles are seen in addition to keratinizing surface-like epithelial configurations. The roles of the epithelial and mesenchymal tissues and the nature of epithelio-mesenchymal interactions in the developing mouse integument are discussed.
TL;DR: Intraocular grafts of chick epithelium combined with mouse molar mesenchyme produced a variety of dental structures including perfectly formed crowns with differentiated ameloblasts depositing enamel matrix, suggesting that the loss of teeth in Aves did not result from a loss of genetic coding for enamel synthesis in the oral epithellium but from an alteration in the tissue interactions requisite for odontogenesis.
Abstract: Intraocular grafts of chick epithelium combined with mouse molar mesenchyme produced a variety of dental structures including perfectly formed crowns with differentiated ameloblasts depositing enamel matrix. The results suggest that the loss of teeth in Aves did not result from a loss of genetic coding for enamel synthesis in the oral epithelium but from an alteration in the tissue interactions requisite for odontogenesis.