Common gene-network links tooth morphogenesis to continuous de novo replacement

Objectives: Most adult dental phenotypes are the result of cyclical rounds of tooth replacement. All known teleost fishes produce unicuspid first generation teeth prior to the induction of a variety of replacement processes (intra and extraosseous). Therefore, complex multicuspid dentitions develop as teeth are replaced. We have taken advantage of the dental diversity of Lake Malawi cichlids to ask how vertebrates generally replace their dentition and how this process acts to influence resulting complex dental phenotypes. Methods: We first identified sets of co-expressed genes active during de novo tooth replacement and tooth morphogenesis. Next, we manipulated targeted pathways with small molecules and demonstrate effects on both tooth replacement and shape. Results: Our data suggest a model wherein the process of tooth replacement is linked to tooth morphogenesis by a common set of gene pathways. This linkage has subsequently been lost or decoupled in mammalian dentitions where complex tooth shapes can appear in first generation dentitions that lack the capacity for lifelong replacement and regeneration. Conclusion: This is the first, large-scale dissection of the genetic and developmental mechanics of vertebrate tooth replacement and its intimate link with morphological diversity.