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Predicting evolutionary patterns of mammalian teeth from development


One motivation in the study of development is the discovery of mechanisms that may guide evolutionary change. Here we report how development governs relative size and number of cheek teeth, or molars, in the mouse. We constructed an inhibitory cascade model by experimentally uncovering the activator–inhibitor logic of sequential tooth development. The inhibitory cascade acts as a ratchet that determines molar size differences along the jaw, one effect being that the second molar always makes up one-third of total molar area. By using a macroevolutionary test, we demonstrate the success of the model in predicting dentition patterns found among murine rodent species with various diets, thereby providing an example of ecologically driven evolution along a developmentally favoured trajectory. In general, our work demonstrates how to construct and test developmental rules with evolutionary predictability in natural systems.

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Figure 1: Hypotheses on the sequential initiation and inhibition of mammalian cheek teeth.
Figure 2: Posterior molars are initiated earlier in vitro when separated from M1.
Figure 3: Initiation of posterior molars can be stimulated by mesenchymal activators.
Figure 4: From molar initiation to predicting molar proportions in murine species.
Figure 5: The inhibitory cascade and the ecological context of murine dental diversity.


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We thank C. K. Chapple, G. Evans, M. Fortelius, I. Salazar-Ciudad, M. Mikkola, I. Thesleff, G. P. Wilson and P. C. Wright for comments, discussions and support with this work; P. Munne, M. Mäkinen, E. Penttilä, I. Pljusnin, R. Santalahti and R. Savolainen for technical help; M. Hyvönen for activin A recombinant protein; C. Tabin and A. Gritli-Linde for the ShhGFPCre mice; and the following museum curators and collection managers for loans: O. Grönwall, R. Asher, M. Hildén and I. Hanski. This study was supported by the Academy of Finland.

Author Contributions K.D.K. and J.J. conceived the study; K.D.K. performed developmental experiments; A.R.E. acquired three-dimensional data; K.D.K., A.R.E. and J.J. performed quantitative analyses; A.R.E. and J.J. constructed the model; A.R.E. performed computer simulations; K.D.K., A.R.E. and J.J. wrote the paper; and J.J. coordinated the study.

The three-dimensional scans for this study are deposited in the MorphoBrowser database, at

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Correspondence to Kathryn D. Kavanagh or Jukka Jernvall.

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Supplementary Information

The file contains Supplementary Figures 1-2 and Legends; Supplementary Tables 1-7 The Supplementary Figures show places of dissection separating M1 from the tails forming posterior molars and growth curves of cultured teeth. The Supplementary Tables list data for the experimental and macroevolutionary analyses and the full results of statistical tests mentioned in the paper. (PDF 980 kb)

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Kavanagh, K., Evans, A. & Jernvall, J. Predicting evolutionary patterns of mammalian teeth from development. Nature 449, 427–432 (2007).

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