Toothsome Signaling Parameters

Science Signaling  30 Mar 2010:
Vol. 3, Issue 115, pp. ec98
DOI: 10.1126/scisignal.3115ec98

Salazar-Ciudad and Jernvall report that fairly simple genetic changes can explain the morphological changes in teeth seen in ringed seals, a species chosen for study because its teeth show a large variation from animal to animal in wild populations. The challenge was to model how changes in genetic makeup could be translated through the process of development into teeth that vary in the number, form, and relative position of the protrusions or cusps that make up the teeth. The authors created a simplified computational model that approximated the processes known to contribute to tooth development. These included an activator that autoregulates and, when it reaches a threshold concentration, then causes cell differentiation and further production of an inhibitor and secondary signals. (In actuality, these virtual molecules are likely encoded by multiple genes such as those producing bone morphogenetic protein 4, activin and inhibin βA subunit (also called Inhba), Wnt family members, and inhibitors like sonic hedgehog.) The model allowed diffusion of gene products among cells and incorporated mechanical interactions of cells that influence the form of the tooth. The model successfully reproduced characteristics of the variation seen in ringed seal teeth in a wild population. By varying the numerical values of genetic or cellular parameters in the model, the authors determined that key parameters that gave different tooth morphologies were the amount of activator and its self-regulation, diffusion of the activator, the strength of the inhibitor and its diffusion properties, and the threshold for the production of the secondary signal. Thus, despite the apparent complexity of such systems, it appears to be possible to integrate developmental models with analysis of genotype and phenotype to explain how genetic variation modulates form, providing new mechanistic insights into development and evolution.

I. Salazar-Ciudad, J. Jernvall, A computational model of teeth and the developmental origins of morphological variation. Nature 464, 583–586 (2010). [PubMed]