Molecular Regulation of Tooth Development

Teeth are present only in vertebrates and parallel the evolutionary appearance of the neural crest. Tooth development represents a classic example of an epithelial-mesenchymal interaction, in this case between the overlying epithelium and underlying neural crest derived mesenchyme. Regulation of tooth patterning from incisors to molars is generated by a combinatorial expression of HOX genes expressed in the mesenchyme. With respect to each tooth's individual development, the epithelium governs differentiation to the bud stage, at which time this regulatory function is transferred to the mesenchyme. Signals for development involve growth factors including: WNTs, bone morphogenetic proteins (BMPs), and fibroblast growth factors (FGFs); the secreted factor sonic hedgehog (SHH); and transcription factors, such as MSX1 and 2 that interact in a complex pathway to produce cell differentiation and patterning for each tooth. Teeth also appear to have a signaling center that represents the "organizer" for tooth development much like the activity of the node during gastrulation (see Chapter 4). This organizer region is called the enamel knot, and it appears in a circumscribed region of the dental epithelium at the tips of the tooth buds. It then enlarges at the cap stage into a tightly packed group of cells but undergoes apoptosis (cell death) and disappears by the end of this stage (Fig. 15.31). While it is present, it expresses FGF-4, SHH, and BMP2 and 4. FGF-4 may regulate outgrowth of cusps much as it participates in limb outgrowth produced by the apical ectodermal ridge (AER); while BMP-4 may regulate the timing of apoptosis in knot cells.

CLINICAL CORRELATES Tooth Abnormalities

Natal teeth have erupted by the time of birth. Usually they involve the mandibular incisors, which may be abnormally formed and have little enamel.

Teeth may be abnormal in number, shape, and size. They may be discolored by foreign substances, such as tetracyclines, or be deficient in enamel, a condition often caused by vitamin D deficiency (rickets). Many factors affect tooth development, including genetic and environmental influences.

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