When patterns are set during embryogenesis, it is expected that they are straightly established rather than subsequently modified. The patterning of the three mouse molars is, however, far from straight, likely as a result of mouse evolutionary history. The first-formed tooth signaling centers, called MS and R2, disappear before driving tooth formation and are thought to be vestiges of the premolars found in mouse ancestors. Moreover, the mature signaling center of the first molar (M1) is formed from the fusion of two signaling centers (R2 and early M1). Here, we report that broad activation of Edar expression precedes its spatial restriction to tooth signaling centers. This reveals a hidden two-step patterning process for tooth signaling centers, which was modeled with a single activator–inhibitor pair subject to reaction–diffusion (RD). The study of Edar expression also unveiled successive phases of signaling center formation, erasing, recovering, and fusion. Our model, in which R2 signaling center is not intrinsically defective but erased by the broad activation preceding M1 signaling center formation, predicted the surprising rescue of R2 in Edar mutant mice, where activation is reduced. The importance of this R2–M1 interaction was confirmed by ex vivo cultures showing that R2 is capable of forming a tooth. Finally, by introducing chemotaxis as a secondary process to RD, we recapitulated in silico different conditions in which R2 and M1 centers fuse or not. In conclusion, pattern formation in the mouse molar field relies on basic mechanisms whose dynamics produce embryonic patterns that are plastic objects rather than fixed end points.

当模式在胚胎发生过程中设定时，人们期望它们是直接建立的，而不是随后修改的。然而，小鼠三颗臼齿的图案远非直线，这可能是小鼠进化历史的结果。最先形成的牙齿信号中心（称为 MS 和 R2）在驱动牙齿形成之前就消失了，被认为是小鼠祖先中发现的前磨牙的遗迹。此外，第一磨牙（M1）的成熟信号中心是由两个信号中心（R2和早期M1）融合形成的。在这里，我们报告Edar表达的广泛激活先于其对牙齿信号中心的空间限制。这揭示了牙齿信号中心隐藏的两步模式化过程，该过程是用单个激活剂-抑制剂对进行反应-扩散（RD）建模的。 Edar表达的研究还揭示了信号中心形成、擦除、恢复和融合的连续阶段。我们的模型中，R2 信号中心并非本质上有缺陷，而是被 M1 信号中心形成之前的广泛激活所消除，该模型预测了Edar突变小鼠中 R2 的令人惊讶的拯救，其中激活减少。离体培养物证实了 R2-M1 相互作用的重要性，表明 R2 能够形成牙齿。最后，通过将趋化性作为 RD 的辅助过程引入，我们在计算机中重现了 R2 和 M1 中心融合或不融合的不同条件。总之，小鼠磨牙区的图案形成依赖于基本机制，其动力学产生的胚胎图案是可塑物体而不是固定端点。