Fig. 8.

Model of revitalization of a diastemal bud. A drawing of a posterior diastemal bud (R₂) at ED 13.5 with a signaling center (gray) at its tip (compare with Fig. 3). Growth inhibitors (e.g. BMP) and growth activators (e.g. SHH, Wnt10, FGF3, FGF4, FGF10, EDA) are distinguished by colors, as in legend (compare with Fig. 1C). We propose that FGF signaling from the mesenchyme can induce expression of FGF4, SHH and EDA, perhaps by the stimulation of the Wnt/LEF1 pathway, and SPRY2 can antagonize this cascade. In wild-type diastemal buds, Spry2 is expressed, the growth-activation pathway is blocked and bud growth is stopped by a relative prevalence of growth inhibitors. The mitotic index is decreased and apoptosis occurs in the epithelium (crosses). In Spry2 mutants, development of the rudimentary bud is not arrested. In contrast to WT embryos, apoptosis is decreased in the rudimentary bud, whereas its mitotic index is as high as in the molar region. Determination of the extent of the contribution of the R₂ rudiment to the supernumerary tooth will require future studies. This model is based on findings reported in this study and on previously reported studies (Hogan, '99; Peterkova et al., 2000, 2003; Zhang et al., 2000; Laurikkala et al., 2001; Kratochwil et al., 2002; Nadiri et al., 2004; Klein et al., 2006; Pummila et al., 2007). ED, embryonic day; BMP, bone morphogenetic protein; FGF, fibroblast growth factor; SHH, Sonic hedgehog; EDA, ectodysplasin; SPRY, sprouty; LEF, lymphoid enhancer binding factor.