Signaling al Dente

Science Signaling  03 Mar 2009:
Vol. 2, Issue 60, pp. ec84
DOI: 10.1126/scisignal.260ec84

In contrast to many other vertebrates, mammals develop only a single row of teeth, and few mutants with supernumerary teeth outside of this single tooth row have been described. Teeth arise from the epidermal dental lamina and are patterned by the underlying mesenchyme, but the mechanism that restricts tooth formation to a single row is largely unexplored. Zhang et al. report that ectopic molar tooth germs formed on the lingual (tongue) side of the dental lamina in mice homozygous for a null allele of odd-skipped related-2 (Osr2), which encodes a zinc finger transcription factor. Although these mutants died shortly after birth due to other physiological defects, tooth germs transplanted from them into renal capsules in adult wild-type mice gave rise to four to five molars, whereas molar tooth germs from wild-type or heterozygous embryos produced only two to three molars. Ectopic expression of early tooth markers in Osr2–/– embryos indicated that the tooth-forming field around the first molars was expanded. In wild-type mice, Osr2 was expressed in the mesenchyme on the lingual side of the dental lamina and in developing teeth in a pattern complementary to that of bone morphogenetic protein 4 (Bmp4), which encodes a growth factor that promotes tooth development. In Osr2–/– embryos, Bmp4 expression expanded into the mesenchyme lingual to the first molar buds, and this mesenchyme induced tooth development in cultured nondental embryonic epithelia. Although Bmp4 expression was reduced in the dental mesenchyme of embryos lacking the homeobox transcription factor Msx1, it was partially restored in Msx1–/–;Osr2–/– double mutants, which do not produce supernumerary teeth. The authors speculate that antagonism between Msx1 and Osr2 in controlling the range of Bmp4 signaling might be one aspect of the tooth patterning system that has been altered to generate the diversity of dentition patterns seen in vertebrates.

Z. Zhang, Y. Lan, Y. Chai, R. Jiang, Antagonistic actions of Msx1 and Osr2 pattern mammalian teeth into a single row. Science 323, 1232–1234 (2009). [Abstract] [Full Text]