Tooth development or odontogenesis is the complex process by which teeth form from embryonic cells, grow, and erupt into the mouth. For human teeth to have a healthy oral environment, all parts of the tooth must develop during appropriate stages of fetal development. Primary (baby) teeth start to form between the sixth and eighth week of prenatal development, and permanent teeth begin to form in the twentieth week. If teeth do not start to develop at or near these times, they will not develop at all, resulting in hypodontia or anodontia. Tooth development or odontogenesis is the complex process by which teeth form from embryonic cells, grow, and erupt into the mouth. For human teeth to have a healthy oral environment, all parts of the tooth must develop during appropriate stages of fetal development. Primary (baby) teeth start to form between the sixth and eighth week of prenatal development, and permanent teeth begin to form in the twentieth week. If teeth do not start to develop at or near these times, they will not develop at all, resulting in hypodontia or anodontia. A significant amount of research has focused on determining the processes that initiate tooth development. It is widely accepted that there is a factor within the tissues of the first pharyngeal arch that is necessary for the development of teeth. The tooth germ is an aggregation of cells that eventually forms a tooth. These cells are derived from the ectoderm of the first pharyngeal arch and the ectomesenchyme of the neural crest. The tooth germ is organized into three parts: the enamel organ, the dental papilla and the dental sac or follicle. The enamel organ is composed of the outer enamel epithelium, inner enamel epithelium, stellate reticulum and stratum intermedium. These cells give rise to ameloblasts, which produce enamel and become a part of the reduced enamel epithelium (REE) after maturation of the enamel. The location where the outer enamel epithelium and inner enamel epithelium join is called the cervical loop. The growth of cervical loop cells into the deeper tissues forms Hertwig Epithelial Root Sheath, which determines the root shape of the tooth. During tooth development there are strong similarities between keratinization and amelogenesis. Keratin is also present in epithelial cells of tooth germ and a thin film of keratin is present on a recently erupted tooth (Nasmyth's membrane or enamel cuticle). The dental papilla contains cells that develop into odontoblasts, which are dentin-forming cells. Additionally, the junction between the dental papilla and inner enamel epithelium determines the crown shape of a tooth. Mesenchymal cells within the dental papilla are responsible for formation of tooth pulp. The dental sac or follicle gives rise to three important entities: cementoblasts, osteoblasts, and fibroblasts. Cementoblasts form the cementum of a tooth. Osteoblasts give rise to the alveolar bone around the roots of teeth. Fibroblasts are involved developing the periodontal ligament which connect teeth to the alveolar bone through cementum. NGF-R is present in the condensing ectomesenchymal cells of the dental papilla in the early cap stage tooth germ and plays multiple roles during morphogenetic and cytodifferentiation events in the tooth. There is a relationship between tooth agenesis and absence of the peripheral trigeminal nerve (see Hypodontia). All stages (bud, cap, bell, crown), growth and morphogenesis of the teeth are regulated by a protein called sonic hedgehog. Various phenotypic inputs modulate the size of the teeth.