Biologists find gene network that gave rise to first tooth

Scientists at the Georgia Institute of Technology have identified a set of genes that they believe was responsible for forming the first teeth in vertebrates. This gene network, (including the genes shh, pitx2 bmp2, bmp4, dlx2, runx2, eda and edar) is believed to have been responsible for the formation of teeth in the throat of the first jawless fish half a billion years ago and are still responsible for the development of teeth in the jaws of all animals today. The research appears online in the journal PLoS Biology beginning 10 February.

'We have identified a core set of genes that probably made the first tooth in these ancient vertebrates and still governs the formation of teeth in modern vertebrates including humans. So it's likely that every tooth made throughout the evolution of vertebrates has used this core set of genes,' said Gareth Fraser, postdoctoral fellow in Georgia Tech's School of Biology.

The first vertebrates to have teeth were a group of eel-like jawless fish known as the conodonts that had teeth not in their mouth, but lining the throat. They're long since extinct, but Fraser, along with J. Todd Streelman, assistant professor in Georgia Tech's School of Biology, investigated the teeth in a group of fish known for their rapid rate of evolution, the cichlids of Africa's Lake Malawi. The cichlids have teeth in both their oral jaws, like humans, and deep in their throats on a pharyngeal jaw. A co-author of the paper, Darrin Hulsey, first identified a surprising positive correlation between the number of teeth in the oral jaw and throat in these fish.

'Originally, I thought there wouldn't be a correlation due to the developmental differences and the evolutionary distinction between the two jaw regions, but it turns out there is,' explained Fraser. 'So fish that have fewer oral teeth also have fewer pharyngeal teeth. This shows that on some level there's a genetic control that governs the number of teeth in both regions.'

The team investigated what this control might be by using a technique localising gene expression in the cells during tooth development, known as insitu hybridisation, and found that a common genetic network governs teeth in both locations.

'So seemingly, regardless of where you grow a tooth, whether it's in the jaw or the pharynx, you use the same core set of genes to do it,' said Streelman. 'We also think it's probable that this network is not just acting in teeth, but also in other similarly patterned structures like hair and feathers.'

In another finding in the same paper, Fraser and colleagues found that a set of genes known as Hox genes, which control where limbs and organs should form during development, are expressed in the teeth and jaws found in the pharynx. It has long been known that Hox genes are not expressed in the oral jaw, and it's widely believed that this lack of expression is responsible for the evolution of the oral jaws. Fraser hypothesised that these Hox genes should be 'switched off' during the formation of the pharyngeal jaw as is the case for the oral jaw. The study shows that this isn't the case.

'The prevailing theory suggests that the loss of Hox genes in the oral region during the transition from jawless to jawed vertebrates facilitated the evolution and diversity of oral jaws. Our data suggest that loss of Hox genes is not an absolute requirement to make a toothed, functional jaw,' said Streelman.

The authors of the study were Gareth J. Fraser, C. Darrin Hulsey, Ryan F. Bloomquist, Kristine Uyesugi, Nancy R. Manley and J. Todd Streelman.