Developing limb or differentiating neural and blood cells are traditional models used to study programmed cell death in mammals. The developing mouse dentition can also be an attractive model for studying apoptosis regulation. Apoptosis is most extant during early odontogenesis in mice. The embryonic tooth pattern is comprised not only of anlagen of functional teeth (incisor, molars), but also of vestiges of ancestral tooth primordia that must be suppressed. Apoptosis is involved in (a) the elimination of vestigial tooth primordia in the prospective toothless gap (diastema) between the incisor and molars and (b) the shaping of germs in functional teeth. This type of apoptosis occurs in the dental epithelium according to a characteristic temporo-spatial pattern. Where apoptosis concentrates, specific signaling is also found. We proposed a hypothesis to explain the stimulation of apoptosis in the dental epithelium by integrating two concepts: (1) The regulation of epithelial budding by positional information generated from interactions between growth-activating and growth-inhibiting signals, and (2) apoptosis stimulation by the failure of death-suppressing signals. During the budding of the dental epithelium, local excess in growth inhibitors (e.g., Bmps) might lead to the epithelial cells' failure to receive adequate growth-activating (apoptosis-suppressing) signals (e.g., Fgfs). The resulting signal imbalance leads to cell "suicide" by apoptosis. Understanding of apoptosis regulation in the vestigial tooth primordia can help to elucidate the mechanism of their suppression during evolution and to identify factors essential for tooth survival. The latter knowledge will be important for developing a technology of tooth engineering.

Institute of Experimental Medicine Academy of Sciences CR Videnska 1083 142 20 Prague 4 Czech Republic

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Three-dimensional analysis of the early development of the dentition

Apoptotic signaling in mouse odontogenesis

Revitalization of a diastemal tooth primordium in Spry2 null mice results from increased proliferation and decreased apoptosis