KAVANAGH, K.D.*; SALAZAR-CUIDAD, I.; JERNVALL, J.; Univ. of Helsinki, Finland; Univ. of Helsinki, Finland; Univ. of Helsinki, Finland: Embryonic Mouse “Braces” Test the Morphodynamic Model of Tooth Evolution

The Morphodynamic Model (Salazar-Cuidad et al., 2003) predicts that shape changes alone could affect the signaling dynamics in the gene networks controlling morphogenesis of the tooth. This computational model is based on known activator-inhibitor gene networks in the tooth primordial. In this in vitro experiment, we enforced a constraint on shape during morphogenesis of the tooth crown in the mouse. The model predicts that cusp-specific signaling centers will be produced closer together simply by reducing growth during early morphogenetic stages, resulting in a vole-like “alternating cusp” pattern using the same gene network that normally produces a “paired cusp” mouse pattern. Embryonic (E14) wild-type mouse tooth germs were dissected and cultured in vitro. Specially designed platinum wire braces were placed on the tissue to prevent lateral growth of the mouse molar tooth germ, thus forcing the mouse tooth germ into approximately the shape of the early vole molar tooth germ at the initiation of cusp morphogenesis. Cultures were photographed 4-5 days later, when cusp patterns were clearly visible. The constrained mouse tooth germs developed cusp fusions as well as cusp patterns suggesting the alternating cusp pattern of the vole. The type of alteration in cusp pattern was related to the distance between the wires (i.e. the severity of the growth limitation). Narrower spaces produced cusp fusions, while slightly wider spaces showed modifications of cusp patterns including the alternating-cusp pattern. Wider spacing produced the normal paired-cusp pattern. These results suggest a high degree of sensitivity in the signal interactions as a consequence of primordium shape alone.