PEDIATRIC ORAL HEALTH 0031-3955/00 $15.00 + .OO NORMAL FORMATION AND DEVELOPMENT DEFECTS OF THE HUMAN DENTITION J. Tim Wright, DDS, MS The development of the human dentition involves a highly orches- trated series of events that are strictly genetically controlled. The devel- opmental timing, location, morphology, structure, and composition of teeth are primarily determined by cascades of molecular events that are regulated by hundreds of genes.4oNormally, humans have 20 primary (i.e., deciduous, or shedding) teeth, which are lost in childhood, and 32 permanent teeth. Dentition begins to form at approximately 6 weeks in utero and continues through late adolescence, when the development of the permanent third molars is completed. Because the development of dentition is prolonged, it is susceptible to environmental influences for many years. A basic understanding of normal dentition and its development allows clinicians to accurately identdy normal and abnor- mal dental conditions and make recommendations for appropriate thera- peutic interventions and patient counseling. Delineating normal from abnormal dental development requires careful evaluation of the patient, including a medical, dental, and family history; clinical examination; and radiographic evaluation and may require special laboratory tests. This article reviews normal dentition and fundamental concepts of tooth development and provides a conceptual framework for diagnosing de- velopmental defects of teeth. From the Department of Pediatric Dentistry, School of Dentistry, The University of North Carolina, Chapel Hill, North Carolina b PEDIATRIC CLINICS OF NORTH AMERICA VOLUME 47 * NUMBER 5 OCTOBER ZOO0 975 976 WRIGHT TOOTH DEVELOPMENT Early embryonic requisites for tooth development include the differ- entiation of the oral ectoderm and the migration of neural crest cells into the craniofacial region, where tooth buds form. By approximately 6 weeks of age (in utero), the oral ectoderm begins to proliferate at the future sites of primary teeth. As the oral ectoderm proliferates, it invaginates into the underlying mesenchyme, where the neural crest- derived ectomesenchymal cells reside.67The continued proliferation and expansion of the oral ectoderm allow the epithelial cells to contact and interact with the underlying ectomesenchymal cells, thereby initiating the development of a tooth bud primordia. These early events in tooth development are largely regulated by the oral epithelium, requiring the expression of numerous genes, including transcription and growth factors.66,@ If these early, epithelial-driven developmental events do not occur, then teeth do not form. This fact has been proven experimentally in transgenic mice, in which transcription factors, such as MSXl and MSX2, were knocked out, after which no teeth developed.40 After tooth formation has been initiated by the invagination of the oral epithelium, the ectodermal cells and the underlying ectomesenchy- ma1 cells engage in a complex series of interactions and signaling mecha- nisms. Instructive biochemical messages regulating cell proliferation, differentiation, and matrix production are transmitted between the ecto- dermal and mesenchymal cells. These interactions result in the differenti- ation of highly specialized cells that produce the unique dental tissues and establish the tooth size and shape. The location and type of tooth (e.g., incisor, cuspid, premolar, or molar) are thought to be genetically determined by the differential combinatorial expression of transcription factors in the regions of the developing teeth.%The oral epithelium gives rise to the enamel organ, which differentiates into the enamel-forming cells, called ameloblasfs. The ectomesenchymal cells give rise to the odon- toblasts, which form the dentin and pulp. The tooth root surface eventu- ally is covered by cementum, which is formed by cementoblasts, which are derived from the mesenchyme. For an intact and viable tooth to develop, each of these cell types must differentiate, produce and process a unique extracellular matrix, and regulate mineralization of the extracel- lular matrix. All of these processes involve strict genetic control, so they represent potential pathways for hereditary defects of teeth, as is discussed later. Numerous excellent and detailed reviews on the mo- lecular control and mechanisms of normal tooth development are avail- able.40.60, 61.68 Teeth are multifunctional appendages participating in diverse func- tions, such as eating and speech. The human dentition also has a crucial role in facial esthetics, so it is important in complex human socialization processes. Dentition provides an efficient masticatory system that allows incising, tearing, and grinding of food. The unique composition and structure of the teeth allows them to survive the tremendous forces and wear associated with mastication. Alteration of the composition or NORMAL FORMATION AND DEVELOPMENT DEFECTS OF HUMAN DENTITION 977 structure of the dental tissues may cause marked alteration of durability, resistance to fracture, and retention in the oral cavity. The composition and structure of teeth give them their unique appearance. The following sections provide a brief overview of each of the dental tissues and some of their important and unique characteristics. DENTAL TISSUES Enamel Dental enamel is the hardest tissue in the human body and provides the fracture-resistant and wear-resistant outer covering for the tooth crown. Enamel is produced by ameloblasts, which secrete a unique extracellular matrix; process this matrix; control the mineralization pro- cess; protect the formed enamel during tooth eruption; and then become a part of the epithelial attachment of the tooth to the gingiva.60Enamel has no regenerative capacity because the ameloblasts are no longer present in the fully formed and erupted tooth. Although the enamel is initially deposited as an organic matrix, it mineralizes by the tightly controlled processing of the extracellular matrix and regulation of cal- cium and phosphate mineral deposition.x Defects in the enamel extracel- lular matrix or its processing may lead to enamel formation that is deficient (hypoplastic) or hyp~mineralized.~~Fully developed enamel consists primarily of carbonate-substituted hydroxyapatite mineral that is highly organized into a unique structure. The apatite molecules are organized into crystallites, which are then arranged and oriented into interlocking prisms (Fig. 1). This complex and highly ordered structure helps to give enamel its incredible strength and wear resistance. Healthy enamel is approximately 96% mineral by weight with about 2% water, 1% protein, and 1% other component^.^^ Alterations in the mineral composition, such as substituting fluorine for carbonate, markedly de- crease the acid solubility of the Changes in the mineral, water, or protein content of enamel result in alteration of the clinical appear- ance, strength, dental caries, and wear resistance of the tissue. Healthy enamel is highly translucent, so much of the color of teeth is derived from the underlying dentin and pulp. Dentin Dentin is the most abundant dental tissue and largely determines the size and shape of teeth. The unique structure and composition of dentin allow it to function as the substructure for the rigid enamel tissue, thereby imparting teeth with the ability to flex and absorb tremendous loads without fracturing. Dentin contains approximately 60% mineral by weight and, unlike enamel, has a substantial organic component (20%). Type 1 collagen is the predominant dentin pr0tein.3~Numerous noncol- 978 WRIGHT Figure 1. Prismatic structure of human enamel (scanning electron micrograph, original magnification x 3000). lagenous proteins are present in dentin, some of which apparently inter- act with collagen to initiate and regulate mineralization.1° Dentin con- tains a complex organization of tubules (Fig. 2) that are approximately 1 Frn in diameter, filled with fluid or the cellular processes of the Figure 2. Odontoblastic processes are seen entering the dentinal tdbules in normal human dentin (scanning electron micrograph, original magnification x 2000). NORMAL FORMATION AND DEVELOPMENT DEFECTS OF HUMAN DENTITION 979 odontoblasts, and are thought to have a role in the neurosensory function of Additional dentin can be deposited along the pulpal wall in a reparative or protective mode secondary to environmental stimuli, such as trauma, tooth wear, or dental caries. Pulp The dental pulp is a specialized tissue comprised of a layer of odontoblasts, fibroblasts, blood vessels, nerves, and a complex extracel- lular matrix. The pulp provides the reparative potential of teeth and neurosensory functi0n.4~The dental pulp can increase the production of dentin (reparative dentin) in an attempt to protect and wall off the vital pulp tissue from injury or noxious stimuli.71Prompt treatments of dental trauma and dental caries are critical steps toward maintaining a healthy vital pulp and allowing an injured or diseased tooth to retain a vital pulp. The pulp continues to lay down small amounts of dentin through- out the life of teeth as a part of the normal pulp physiology.64 This process results in a smaller pulp chamber as people age and is part of the reason that teeth continue to yellow with age. It is critical to maintain a healthy dental pulp until the root is fully formed and its walls are of adequate thickness to maintain the tremendous forces transmitted from the crown during function. If the pulp becomes