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Antagonistic actions of Msx1 and Osr2 pattern mammalian teeth into a single row - PubMed

  • ️Thu Jan 01 2009

Antagonistic actions of Msx1 and Osr2 pattern mammalian teeth into a single row

Zunyi Zhang et al. Science. 2009.

Abstract

Mammals have single-rowed dentitions, whereas many nonmammalian vertebrates have teeth in multiple rows. Neither the molecular mechanism regulating iterative tooth initiation nor that restricting mammalian tooth development in one row is known. We found that mice lacking the transcription factor odd-skipped related-2 (Osr2) develop supernumerary teeth lingual to their molars because of expansion of the odontogenic field. Osr2 was expressed in a lingual-to-buccal gradient and restricted expression of bone morphogenetic protein 4 (Bmp4), an essential odontogenic signal, in the developing tooth mesenchyme. Expansion of odontogenic field in Osr2-deficient mice required Msx1, a feedback activator of Bmp4 expression. These findings suggest that the Bmp4-Msx1 pathway propagates mesenchymal activation for sequential tooth induction and that spatial modulation of this pathway provides a mechanism for patterning vertebrate dentition.

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Figures

Fig. 1
Fig. 1

(A, B) Frontal sections of E18.5 wildtype (A) and Osr2−/− (B) littermates. Arrows in B point to supernumerary tooth germs. (C) Frontal section of wildtype first molar region at E13.5. (D–F) Frontal sections of Osr2−/− mutant first molar regions at E13.5, E15.5 and E16.5. Arrows point to supernumerary tooth germs. (G, H) Mineralized teeth from renal capsule cultures of E13.5 wildtype (G) and Osr2−/− (H) molar tooth germs. m1, first molar tooth germ; to, tongue. Scale bar, 100 µm.

Fig. 2
Fig. 2

Expression patterns of Osr2 (A–D) and Bmp4 (E–H) mRNAs along the buccolingual axis of mouse molar tooth germs at E11.5 (A, E), E12.5 (B, F), E13.5 (C, G), and E14.5 (D, H). Lingual side is to the left in all panels. Black dashed lines mark the boundary between dental epithelium and mesenchyme. ps, palatal shelf.

Fig. 3
Fig. 3

(A, B) Bmp4 mRNA expression in E13.5 wildtype (A) and Osr2−/− (B) first molar tooth germs. Arrows in B point to lingually expanded Bmp4 expression. (C, D) Increased levels of phospho-Smad1 accompany the supernumerary dental placode (arrow in D) in an E14.5 Osr2−/− embryo, compared with wildtype littermate (C). (E, F) Isolated molar tooth mesenchyme from E13.5 wildtype (E) and Osr2−/− (F) embryos induced tooth formation from E10.5 second branchial arch epithelia. (G, H) Isolated mesenchyme lingual to E13.5 molar tooth germ of Osr2−/− (H), but not that of wildtype (G), induced tooth formation from E10.5 second branchial arch epithelia. White dashed lines in E–H mark the boundary between epithelium and mesenchyme. Insets show sections of renal capsule cultures of corresponding recombinant explants. Numbers in E–H indicate the ratios of corresponding recombinant explants forming teeth in renal capsules. m1, first molar tooth bud; ps, palatal shelf; T, tooth in renal capsule.

Fig. 4
Fig. 4

(A–C) Frontal sections through the first molar tooth germs (arrows) of E18.5 wildtype (A), Msx−/− (B), and Msx1−/−Osr2−/− (C) embryos. (D–I) Bmp4 mRNA expression in the first molar tooth mesenchyme (arrows) in wildtype (D, G), Msx1−/− (E, H), and Msx1−/−Osr2−/− (F, I) embryos at E13.5 (D–F) and E14.5 (G-I). (J–L) Lef1 mRNA expression in the first molar tooth mesenchyme (arrows) in E15 wildtype (J), Msx1−/− (K), and Msx1−/−Osr2−/− (L) littermates. ps, palatal shelf; to, tongue. Scale bar, 200 µm.

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