One of the remaining challenges for evolutionary developmental studiesof mammals, whose evolution is best known from their teeth, is howtheir tooth shape is altered during development. Researchers of theUniversity of Helsinki together with their Japanese colleagues from theUniversity of Kioto now propose a 'balance of induction' mechanismdirecting the placement of tooth shape features called cusps. Positionand shape of cusps determine whether a tooth shape belongs to human ormouse, for example. Whereas developmental initiation of cusp formationis known to involve several developmental genes at the places of futurecusps, it has remained unknown how cusps form at the right places.
Computer simulations on tooth development have suggested that thereshould be a gene inhibiting induction of cusps. The research team hasnow identified this inhibitor to be a recently identified gene calledectodin. It turned out that ectodin is the first gene that is expressedas a mirror image of the future cusps.
The team generated a mouse that has no functional ectodin. Whereas themice appear fairly normal, the areas forming cusps were much broaderresulting in cheek teeth whose shape resembles more rhinoceros teeththan mouse teeth. Furthermore, these mice have extra teeth andsometimes adjacent teeth are fused. These results indicate that thereis a delicate balance of induction and inhibition in determining toothcusps and that ectodin is a key gene in this developmental control.
The team confirmed the importasnce of ectodin to development of teethby culturing teeth that produce ectodin and teeth that lack ectodinwith excess amounts of cusp inducing protein (bone morphogeneticprotein or BMP). Whereas teeth producing ectodin develop quite normallywith excess BMP, teeth without ectodin had a markedly acceleratedinduction of cusps. Indeed the researchers were able to induce cuspsand mineralization of teeth much faster than happens in normal mouseteeth, suggesting that tinkering with the balance of cusp induction mayhold potential for future tissue engineering of hard tissues.
Article: Regulation of mammalian tooth cusp patterning by ectodin.
Yoshiaki Kassai, Pauliina Munne, Yuhei Hotta, Enni Penttilä, KathrynKavanagh, Norihiko Ohbayashi, Shinji Takada, Irma Thesleff, JukkaJernvall, Nobuyuki Itoh.
Science, Sept. 23, 2005
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