Figure 5

A tentative model of molecular control of formation and inhibition of supernumerary tooth development in mouse lower diastema in Spry2;Spry4 mutants. In wild-type mouse embryos (A), Spry2/Spry4 antagonizes Fgf signaling [13] and thus indirectly influences Shh level [13,31,39]. Shh is a negative regulator of Wnt [18] and plays a role in tooth separation [43]. In Spry2;Spry4 mutants (B) loss of function of the Sprouty genes leads to increasing of FGF signaling [13,34,39]. This results in a reduction of apoptosis and stimulation of cell proliferation in the MS and R2 rudiments, which results in the formation of the supernumerary tooth primordium [31,37]. Higher level of Fgf causes a higher level of Shh, which helps R2 rudiment to separate from M1 tooth germ. However, the elevated Shh strongly inhibits the Wnt signaling, decreased Wnt signaling cannot prevent an independent development of R2 rudiment as supernumerary tooth primordium, which finally regresses. The thickness of lines and frames symbolizes approximate levels of signaling activity.