Experimental research on tooth development or odontogenesis is based very largely on the teeth of murine rodents (Butler 1967). Pioneering work by Shirley Glasstone on rat tooth germ cultures gave detailed information about structural, histological, and self-differentiating interactions of explants (Glasstone 1936). However, the dentition of the mouse and that of many other mammals is very different. Mice have highly specialized incisors, distinctive molar patterns, a small number of teeth, and they do not have tooth replacement (Butler 1967).

In vertebrate embryos, a group of cells, called neural crest (NC) cells, separate from the neural tube and migrate away from their parental epithelium to reaggregate with other cells. In the developing embryo, almost all organs, glands, and tissues, such as craniofacial skeleton, cornea, teeth/dentin, thyroid gland, thymus, cardiac septa, adrenal gland, melanocyte, autonomic nerve, sensory nerve, and Schwann cells, have these basic cells (Crane and Trainor 2006; Alberts et al. 2008; Lee et al. 2010a). In addition to the unique invasiveness of NC cells, their contribution toward building the head of vertebrates has been considered to be a turning point in the evolution of the vertebrates (Gans and Northcutt 1983).

Although NC cells are of ectodermal origin, it has been suggested to call them “mesectoderm” or “ectomesenchyme” since they undergo “mesenchymalization.” This property is important to discussions regarding mesenchymal stem cells since their origin is mesenchyme, which is derived from the mesodermal germ layer (Le Douarin et al. 2004). On the other hand, along with the cranial skeleton and other tissues of the head and neck, odontoblasts and tooth papillae are derived from mesectoderm or ectomesenchym (Le Douarin et al. 2004). Oral ectomesenchymal and ectodermal inductive interactions are the earliest expressions recorded in vertebrate fossils. These epithelial (oral ectoderm) and mesenchymal (ectomesenchyme/mesectoderm) interactions phylogenetically precede the origin of odontogenesis (Moss 1969).

Teeth share similarities with the other ectodermal organs, such as hair, feathers, scales, beaks, and many exocrine organs, in the placode and bud stage. These similarities disappear by morphogenesis. Initiation of tooth development includes a series of sequential reciprocal inductive molecular interactions between the dental epithelium and the underlying ectomesenchymal cells (Jernvall et al. 2000). While the first signal inducing differentiation comes from the mesenchyme in all ­ectodermal organs, in tooth development, morphogenetic events are started by the signals from the epithelium (Pispa and Thesleff 2003). Several recombination studies revealed that only the very early first arch epithelium cells (occurring during the 8–11.5th embryonic days (ED) of mouse development) and ectomesenchyme (ED 12) have odontogenic potential (Mina and Kollar 1987; Lemus 1995).

The molecular aspects of tooth development are similar to those in the development of other organs and include epithelial–mesenchymal interactions. A plethora of molecules (approximately 300) are involved in tooth development such as fibroblast growth factors (FGFs), bone morphogenetic proteins (BMPs), sonic hedgehog (SHH), and wingless integrated (WNTs). As mentioned previously, BMP4 acts antagonistically with FGF8 and this interaction plays a role in the periodic patterning (Neubuser et al. 1997). Irma Thesleff’s group from the University of Helsinki has been working on the key features of dental development. Their web site, http://bite-it.helsinki.fi/, includes a wide range of data largely originating in previously published reports and is thus a compilation of the work of the researchers in this field. The web site provide a source for the expressions of growth factors, receptors, signaling molecules, transcription factors, intracellular molecules, extracellular molecules, and plasma membrane molecules during the different stages of tooth development in mice, rats, humans, and other species. The molecular dialogue between oral ectoderm and odontogenic mesenchyme during tooth development is very complicated (Fig. 2.1) (Jernvall and Thesleff 2000). There is a vast knowledge about the signal interchanges that are crucial to control differentiation and morphological changes and spatiotemporal expression of specific genes during teeth formation, yet little is known about the regulation of the signals (i.e., down or up) (Tucker and Sharpe 2004). All of the data show that there is no single gene that is directly connected with ontogenesis or the lack of any specific tooth. Instead, tooth initiation and morphogenesis occur by an orchestration of numerous genetic and epigenetic factors (Jernvall and Thesleff 2000; Koussoulakou et al. 2009). At the same time, most of the developmental defects in teeth usually occur as a result of mutations in genes encoding signaling molecules and transcription factors (Koussoulakou et al. 2009), such as mutations in the PAX9 gene resulting in partial or total anadontia and mutations in RUNX2 causing supernumerary teeth (Peters et al. 1998; Ryoo et al. 2010).