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Introductiony The organization and renewal capacity of teeth vary

greatly among vertebrates. Mammals have only one rowof teeth that are renewed at most once, whereas many nonmammalian species have multi rowed dentitions and show

remarkable capacity to replace their teeth throughout life.

y Although knowledge on the genetic basis of toothmorphogenesis has increased exponentially over the past

20 years, little is known about the molecular mechanismscontrolling sequential initiation of multiple tooth rows or restricting tooth development to one row in mammals.

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OSR 2 geney P rotein odd-skipped-related 2 is a protein that in humans

is encoded by the OSR2 gene.

y O dd-skipped related 2 ( O sr2) is expressed in the domainof epithelialmesenchymal interactions during tooth andkidney development.

y In mice, it is involved in the development of the palateand in suppressing the formation of teeth after the eruptionof adult teeth .

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E xperiment by Jiang and colleagues

y They generated mice that lacked the oddskipped related-2(O sr2) gene.

y Deleting the O sr2 gene resulted in cleft palate, a birth

defect where the two halves of the roof of the mouth failto join up properly, leaving a gap.

y Also, the O sr2 "knockout" mice developed teeth outsideof the normal tooth row.

y Jiang decided to focus his research first on the effect of O sr2 on teeth patterning (vs. cleft palate) because muchmore was known at the time about teeth development

pathways.

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y E xperiments, showed that the developing tooth mesenchyme wascapable of inducing tooth formation from epithelial tissues that

normally would not participate in tooth development.

y Researchers confirmed that it was indeed the mesenchyme that carriedtooth initiation signals later in development, but how those signals wererestricted to the area beneath the tooth row was unknown.

y P ast studies in other labs had shown bone morphogenic protein 4(BM P 4) to be an important factor for the initiation of teeth, and that a

protein called Msx1 amplifies the BM P 4 tooth-generating signal.

y The current study provides the first solid proof that the precise spacewhere mammals can develop teeth (the "tooth morphogenetic field") isshaped and restricted by the effect of O sr2 on the expression of theBmp4 gene within the mesenchymal cell layer.

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y Jiang and colleagues also engineered a group of mice with both the O sr2 and Msx1 genes removed.

y While mice without Msx1 failed to grow any teeth, micelacking both Msx1 and O sr2 grew the first molars, but noadditional teeth.

y Thus, without O sr2, enough BM P 4 was expressed for thefirst molar teeth to grow, but without Msx1, the BM P 4signal was not amplified to the point where it could kick

off the next tooth in the row.