Meeting Abstract

66.4  Tuesday, Jan. 6  Tinkering with ectodysplasin reveals the dynamic basis of tooth development and morphology HARJUNMAA, E.**; THESLEFF, I.; JERNVALL, J.; Institute of Biotechnology, University of Helsinki, Finland. enni.harjunmaa@helsinki.fi

It is often thought that tinkering with signaling networks produces small changes in development, leading to phenotypic variation, and ultimately to evolutionary change. We have experimented on such tinkering by controlling the amount of the signaling factor Ectodysplasin (Eda) during mammalian tooth development. Tabby-mice lack functional Eda, and consequently have abnormally small molars with a simplified cusp pattern. In order to study in detail the developmental variation between wild-type- and Tabby-teeth, we have made time-lapse monitoring of Tabby-molars cultured in different concentrations of Eda-protein. Our Tabby-line has been crossed with transgenic mice that express Green Fluorescent Protein (GFP) under a Sonic Hedgehog (Shh) promoter. Shh, and thus GFP, is expressed in the signaling centers of the tooth, the enamel knots, which direct growth and give rise to individual cusps. Adding Eda into the culturing media of Tabby-teeth increased their rates of growth and development, apparently through enhancing the performance of the enamel knots. The results show that most enamel knots form in the Tabby-molar, but the poor growth rate fails to accommodate all of them, leading to the simplification of the cusp pattern. Increasing the dosage of Eda caused a gradual expansion in crown dimensions and a stepwise increase in the number of cusps. The enamel knots were initiated in a specific order, which largely reflected the evolutionary order of cusp appearance. Consequently, it was possible to engineer morphologies reminiscent of known evolutionary transitions. These results suggest that the Eda signaling pathway may have provided the material (or the target) for natural selection to modify tooth morphology during mammal evolution.