Fig. 6.
Simultaneous promotion of overall growth and inhibition of cusp patterning by IGF1 provides a mechanism to scale teeth. (A) Mouse molars treated with IGF1 protein for 6 h show upregulation (orange) of 12 DNA replication markers (GO:0006260), n = 5 for both the treatments and controls. (B) In contrast to growth-promoting effects (A), genes required for normal tooth development show only downregulation in IGF1-treated molars (down-regulated genes in purple). Enamel knot expressed genes are in bold. Horizontal line denotes Padj = 0.05. Volcano plots are zoomed to the genes of interest, see SI Appendix, Fig. S2, for the overall fold enrichment of GO categories. (C) Computer simulations of molar development using ToothMaker show that changing proliferation rate (Mgr) or activator autoregulation (Act) alone changes the pattern (forming secondary enamel knot regions shown in red). By increasing growth and by decreasing activation, which mimic the effects in A and B, the simulated mouse tooth can be scaled up. See text and Materials and Methods for details.