1. Evolution & Development Unit, Institute of Biotechnology, PO Box 56 (Viikinkaari 9), FIN-00014 University of Helsinki, Finland
2. Department of Ecology and Evolution, Stony Brook University, Stony Brook, New York 11794, USA
3. Present address: School of Marine and Atmospheric Sciences, Stony Brook University, Stony Brook, New York 11794, USA.

Correspondence to: Kathryn D. Kavanagh^1,3Jukka Jernvall^1,2 Correspondence and requests for materials should be addressed to K.D.K. (Email: kathryn_kavanagh@yahoo.com) or J.J. (Email: jernvall@fastmail.fm).

Abstract

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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