Rosen—Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism Se 904 Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism, Eighth Edition. Edited by Clifford J. Rosen. © 2013 John Wiley & Sons, Inc. Published 2013 by John Wiley & Sons, Inc. INTRODUCTION Tooth development or odontogenesis is the complex process by which dental mineralized tissues form from embryonic cells that differentiate into ameloblasts that secrete enamel, odontoblasts that produce dentin, and cementoblasts that make cementum. Enamel is of epi- thelial origin and covers the crown of each tooth. In contrast, dentin and cementum are of mesenchymal origin. Dentin forms the bulk of the tooth and extends within both the crown and root. It has a yellow color, in contrast to the much whiter and harder enamel. Cemen- tum is deposited only in the root area on the recently mineralized dentin matrix. The tooth is anchored onto its socket (alveolar bone) by the periodontal ligament (PDL), a connective tissue structure that surrounds the tooth root and connects each tooth to the alveolar bone through a specialized set of collagen fibers. STAGES OF TOOTH MORPHOGENESIS AND ITS MOLECULAR CONTROL Mammalian teeth have distinctive crown and root mor- phologies, which are highly adapted to their particular masticatory function. The generation of individual teeth relies upon interactions between the oral epithelium and mesenchymal cells that are derived from the cranial neural crest cells (CNCCs). Their formation involves a precisely orchestrated series of molecular and morphoge- netic events. Although many diverse types of teeth exist in different species, non-human tooth development is largely the same as in humans. Therefore, we have used here examples of mouse tooth development as a proto- type model for understanding human tooth formation. When possible we tried to make connections to human pathologies. Morphologically, tooth development begins with a thickening of the oral epithelium that forms a structure known as the dental lamina. Within the dental lamina, cells start to proliferate and to invaginate the underlying mesenchyme in precise positions to form the dental plac- odes (which define where the teeth will be positioned into the jaws). Tooth development proceeds through a series of morphological stages that necessitate sequential and reciprocal interactions between the oral epithelium and the underlying cranial neural crest-derived mesen- chyme. In mice, the oral epithelium starts thickening at the embryonic day 10.5 (E10.5) and progressively acquires the bud (E13.5), cap (E14.5), and bell (E16.5) configura- tions (Fig. 109.1). At the bell stage, two mesenchymal cell populations can be distinguished: the dental follicle and dental pulp. Dental pulp cells adjacent to the dental epithelium differentiate into odontoblasts, while epithe- 109 Development and Structure of Teeth and Periodontal Tissues Petros Papagerakis and Thimios Mitsiadis Introduction 904 Stages of Tooth Morphogenesis and Its Molecular Control 904 Signals Controlling Dental Cell Differentiation 906 Dental Mineralized Tissues Formation 906 Stem Cells During Tooth Repair 911 Conclusion 911 Acknowledgements 912 References 912 Rosen_3889_c109_main.indd 904 3/18/2013 3:34:14 PM