Abstract
Fungiform taste papillae form a regular array on the dorsal tongue. Taste buds arise from papilla epithelium1 and, unusually for epithelial derivatives, synapse with neurons, release neurotransmitters and generate receptor and action potentials2,3. Despite the importance of taste as one of our five senses, genetic analyses of taste papilla and bud development are lacking. We demonstrate that Wnt-β-catenin signaling is activated in developing fungiform placodes and taste bud cells. A dominant stabilizing mutation of epithelial β-catenin causes massive overproduction of enlarged fungiform papillae and taste buds. Likewise, genetic deletion of epithelial β-catenin or inhibition of Wnt-β-catenin signaling by ectopic dickkopf1 (Dkk1)4,5,6 blocks initiation of fungiform papilla morphogenesis. Ectopic papillae are innervated in the stabilizing β-catenin mutant, whereas ectopic Dkk1 causes absence of lingual epithelial innervation. Thus, Wnt-β-catenin signaling is critical for fungiform papilla and taste bud development. Altered regulation of this pathway may underlie evolutionary changes in taste papilla patterning.
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Change history
07 December 2006
In the version of this article initially published online, the label in the lower-left corner of Figure 6b was incorrect. The correct label is 'Act β-catenin'. This error has been corrected for all versions of the article.
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Acknowledgements
We thank E. Fuchs (Rockefeller University) for Tg(Fos-lacZ)34Efu reporter mice, A. Glick (Penn State University) for KRT5-rtTA mice, L. Ash for histology and M. Wright and C. Liggins for technical assistance. S.E.M. is supported by US National Institutes of Health grants R01-AR47709 and R01-DE015342, L.A.B. by R01-DC003947, A.A.D. by RO1-AR45973, S.H.Y. by T32-HD007505 and C.L.S.-C. by T32-HL007312. N.M.G. and S.T.R. were supported by T32-AR007465. R.T.M. is an investigator of the Howard Hughes Medical Institute.
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Contributions
The study was designed by F.L., S.T., N.M.G., L.A.B. and S.E.M. In situ hybridizations were carried out by F.L., S.T. and S.T.R. Immunofluorescence staining was carried out by F.L., S.H.Y. and S.T. X-gal staining was performed by F.L., S.T. and C.L.S.-C. Organ culture experiments were performed by S.T. Ctnnb1(Ex3)fl mice were provided by M.M.T. KRT14-Cre Ctnnb1(Ex3)fl/+ mice were generated by F.L., S.T., S.H.Y. and A.A.D. KRT5-rtTA tetO-Dkk1 mice were generated by F.L. and T.A. KRT14-Cre Ctnnb1fl/fl mice were generated by N.M.G. and F.L. F.L. and N.M.G. performed scanning electron microscopy analyses. R.T.M. was involved in study design and discussion of results. The manuscript was written by F.L., R.T.M., L.A.B. and S.E.M.
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Supplementary information
Supplementary Fig. 1
Wnt genes are expressed in embryonic tongue epithelium. (PDF 1083 kb)
Supplementary Fig. 2
K14-Cre is active in tongue epithelium by E12.5 (PDF 511 kb)
Supplementary Fig. 3
Expression of Bmp4 is elevated in K14-Cre Ctnnb1lox(ex3) tongue epithelium compared with control littermate tongue epithelium at E18.5. (PDF 1053 kb)
Supplementary Fig. 4
Wnt and β-catenin signaling is required for expression of fungiform placode markers. (PDF 1833 kb)
Supplementary Table 1
Primers used for genotyping gene-targeted and transgenic mice. (PDF 43 kb)
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Liu, F., Thirumangalathu, S., Gallant, N. et al. Wnt-β-catenin signaling initiates taste papilla development. Nat Genet 39, 106–112 (2007). https://doi.org/10.1038/ng1932
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DOI: https://doi.org/10.1038/ng1932
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