Researchers of the University of Helsinki together with their Japanese colleagues from the Kyoto University now propose a 'balance of induction' mechanism directing the placement of tooth shape features called cusps. Position and shape of cusps determine whether a tooth shape belongs to human or mouse, for example. Whereas developmental initiation of cusp formation is known to involve several developmental genes at the places of future cusps, it has remained unknown how cusps form at the right places.
Computer simulations on tooth development have suggested that there should be a gene inhibiting induction of cusps. The research team has now identified this inhibitor to be a recently identified gene called ectodin. It turned out that ectodin is the first gene that is expressed as a mirror image of the future cusps.
The team generated a mouse that has no functional ectodin. Whereas the mice appear fairly normal, the areas forming cusps were much broader resulting in cheek teeth whose shape resembles more rhinoceros teeth than mouse teeth. Furthermore, these mice have extra teeth and sometimes adjacent teeth are fused. These results indicate that there is a delicate balance of induction and inhibition in determining tooth cusps and that ectodin is a key gene in this developmental control.
The team confirmed the importasnce of ectodin to development of teeth by culturing teeth that produce ectodin and teeth that lack ectodin with excess amounts of cusp inducing protein (bone morphogenetic protein or BMP). Whereas teeth producing ectodin develop quite normally with excess BMP, teeth without ectodin had a markedly accelerated induction of cusps. Indeed the researchers were able to induce cusps and mineralization of teeth much faster than happens in normal mouse teeth, suggesting that tinkering with the balance of cusp induction may hold potential for future tissue engineering of hard tissues.
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In their new work, Shimeld and colleagues approached this question by examining the evolutionary origin of one crystallin protein family, known as the -crystallins. Focusing on sea squirts, invertebrate cousins of the vertebrate lineage, the researchers found that these creatures possess a single crystallin gene, which is expressed in its primitive light-sensing system. The identification of the sea squirt's crystallin strongly suggests that it is the single gene from which the vertebrate -crystallins evolved.
The researchers also found that, remarkably, expression of the sea squirt crystallin gene is controlled by genetic elements that also respond to the factors that control lens development in vertebrates: The researchers showed that when regulatory regions of the sea squirt gene are transferred to frog embryos, these regulatory elements drive gene expression in the tadpoles' own visual system, including the lens. This strongly suggests that prior to the evolution of the lens, there was a regulatory link between two tiers of genes: those that would later become responsible for controlling lens development, and those that would help give the lens its special physical properties. This combination of genes appears to have then been co-opted in an early vertebrate during the evolution of its visual system, giving rise to the lens.
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