Evo-Devo Regulation and Coordination of Vertebrate Dentitions and Jaws

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Eating is of course essential to survival. A core question driving studies of primate, mammalian and vertebrate evolution is how different head sizes and shapes arose without compromising vital head functions and structures (e.g., teeth and the jaws that hold them). To eat, hunt, and ultimately survive to raise offspring, an animal's teeth and jaws must develop properly in the right place, at the right time. Despite their importance for survival, the developmental-genetic processes that coordinate tooth and jaw growth remain a mystery. Explaining these processes is vital to understand how species develop, evolve and adapt to a variety of foods. In some species, including humans, teeth and jaws are also important for functions beyond eating, such as making sounds and facial expressions. Also, human tooth and jaw evolution is likely entwined with cultural evolution, notably tool-use and cooking. The long term objective of my NSERC-funded research program is to determine the extent to which dental and jaw tissues influence each other's development and, putatively, evolution. My trainees and I will examine this question using a mouse model system where a mutation of the gene, p63, leads to the failure of teeth to develop in the jaw. By experimentally "removing teeth from the equation", already we have identified for the first time a network of genes that appear to regulate tooth formation with virtually no impact on lower jaw formation. This gene network could allow teeth to evolve without risking lethal change to the jaw skeleton. Now, we seek to determine exactly where and when these genes-of-interest are active in the embryonic tooth, and which genes in the network speak directly, or indirectly, to each other and are directed by the p63 gene, a “master regulator”. In this way, we will assemble the pieces of this particular gene regulatory network. We will use our new knowledge about where exactly in developing teeth these genes are active to experimentally determine their particular functions, which are still not known. In creating this new knowledge about the genetics of tooth formation, we will fill a long-standing gap in our collective understanding of how diversity arose among vertebrates living and extinct. My novel research program will involve training outstanding undergraduate and graduate students over the five-year funding period, providing my students with the highly-desired professional skills necessary to make them competitive for jobs in research and other Canadian career sectors such as education, government, industry and communication. We will use our unique scientific insights to more accurately model how animal faces and heads develop and evolve. In the future, we will expand our model of hard tissues (bones, teeth) to test how soft tissues such as muscles change alongside bones, allowing different species to use their mouths in specific ways to hunt or forage for a variety different food types.**