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Wnt-β-catenin signaling initiates taste papilla development

Nature Genetics volume 39, pages 106–112 (2007)Cite this article

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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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Figure 1: Wnt10b mRNA expression and Wnt-β-catenin signaling activity localize to developing fungiform papillae.
Figure 2: Stimulation of Wnt-β-catenin signaling ex vivo promotes fungiform placode fate.
Figure 3: Mutation of epithelial β-catenin to a stabilized form promotes fungiform papilla and taste bud development in vivo.
Figure 4: Wnt-β-catenin signaling is required for expression of fungiform placode markers.
Figure 5: Wnt-β-catenin signaling is required for the development of fungiform papillae.
Figure 6: Wnt-β-catenin signaling controls tongue epithelial innervation.

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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.

References

  1. Stone, L.M., Finger, T.E., Tam, P.P. & Tan, S.S. Taste receptor cells arise from local epithelium, not neurogenic ectoderm. Proc. Natl. Acad. Sci. USA 92, 1916–1920 (1995).

    Article  CAS  Google Scholar 

  2. Sugimoto, K. & Teeter, J.H. Voltage-dependent ionic currents in taste receptor cells of the larval tiger salamander. J. Gen. Physiol. 96, 809–834 (1990).

    Article  CAS  Google Scholar 

  3. Roper, S. Regenerative impulses in taste cells. Science 220, 1311–1312 (1983).

    Article  CAS  Google Scholar 

  4. Zorn, A.M. Wnt signalling: Antagonistic Dickkopfs. Curr. Biol. 11, R592–R595 (2001).

    Article  CAS  Google Scholar 

  5. Andl, T., Reddy, S.T., Gaddapara, T. & Millar, S.E. WNT signals are required for the initiation of hair follicle development. Dev. Cell 2, 643–653 (2002).

    Article  CAS  Google Scholar 

  6. Chu, E.Y. et al. Canonical WNT signaling promotes mammary placode development and is essential for initiation of mammary gland morphogenesis. Development 131, 4819–4829 (2004).

    Article  CAS  Google Scholar 

  7. Hall, J.M., Hooper, J.E. & Finger, T.E. Expression of sonic hedgehog, patched, and Gli1 in developing taste papillae of the mouse. J. Comp. Neurol. 406, 143–155 (1999).

    Article  CAS  Google Scholar 

  8. Zhou, Y., Liu, H.X. & Mistretta, C.M. Bone morphogenetic proteins and noggin: Inhibiting and inducing fungiform taste papilla development. Dev. Biol. 297, 198–213 (2006).

    Article  CAS  Google Scholar 

  9. Mistretta, C.M. Developmental neurobiology of the taste system. in Taste and Smell in Health and Disease (ed. Getchell, T.V.) 35–64 (Raven, New York, 1991).

  10. Cadigan, K.M. & Liu, Y.I. Wnt signaling: complexity at the surface. J. Cell Sci. 119, 395–402 (2006).

    Article  CAS  Google Scholar 

  11. Gat, U., DasGupta, R., Degenstein, L. & Fuchs, E. De novo hair follicle morphogenesis and hair tumors in mice expressing a truncated β-catenin in skin. Cell 95, 605–614 (1998).

    Article  CAS  Google Scholar 

  12. Huelsken, J., Vogel, R., Erdmann, B., Cotsarelis, G. & Birchmeier, W. β-catenin controls hair follicle morphogenesis and stem cell differentiation in the skin. Cell 105, 533–545 (2001).

    Article  CAS  Google Scholar 

  13. Noramly, S., Freeman, A. & Morgan, B.A. β-catenin signaling can initiate feather bud development. Development 126, 3509–3521 (1999).

    CAS  PubMed  Google Scholar 

  14. Okubo, T., Pevny, L.H. & Hogan, B.L. Sox2 is required for development of taste bud sensory cells. Genes Dev. 20, 2654–2659 (2006).

    Article  CAS  Google Scholar 

  15. DasGupta, R. & Fuchs, E. Multiple roles for activated LEF/TCF transcription complexes during hair follicle development and differentiation. Development 126, 4557–4568 (1999).

    CAS  PubMed  Google Scholar 

  16. Hedgepeth, C.M. et al. Activation of the Wnt signaling pathway: a molecular mechanism for lithium action. Dev. Biol. 185, 82–91 (1997).

    Article  CAS  Google Scholar 

  17. Harada, N. et al. Intestinal polyposis in mice with a dominant stable mutation of the β-catenin gene. EMBO J. 18, 5931–5942 (1999).

    Article  CAS  Google Scholar 

  18. Andl, T. et al. Epithelial Bmpr1a regulates differentiation and proliferation in postnatal hair follicles and is essential for tooth development. Development 131, 2257–2268 (2004).

    Article  CAS  Google Scholar 

  19. Byrne, C., Tainsky, M. & Fuchs, E. Programming gene expression in developing epidermis. Development 120, 2369–2383 (1994).

    CAS  PubMed  Google Scholar 

  20. Soriano, P. Generalized lacZ expression with the ROSA26 Cre reporter strain. Nat. Genet. 21, 70–71 (1999).

    Article  CAS  Google Scholar 

  21. Miura, H. et al. Co-expression pattern of Shh with Prox1 and that of Nkx2.2 with Mash1 in mouse taste bud. Gene Expr. Patterns 3, 427–430 (2003).

    Article  CAS  Google Scholar 

  22. Zhang, G.H., Deng, S.P., Li, L.L. & Li, H.T. Developmental change of α-gustducin expression in the mouse fungiform papilla. Anat. Embryol. (Berl.), published online 25 August 2006 (doi: 10.1007/s00429–006–0112–2).

  23. Brault, V. et al. Inactivation of the β-catenin gene by Wnt1-Cre-mediated deletion results in dramatic brain malformation and failure of craniofacial development. Development 128, 1253–1264 (2001).

    CAS  PubMed  Google Scholar 

  24. Northcutt, R.G. & Barlow, L.A. Amphibians provide new insights into taste-bud development. Trends Neurosci. 21, 38–43 (1998).

    Article  CAS  Google Scholar 

  25. Mbiene, J.P. & Mistretta, C.M. Initial innervation of embryonic rat tongue and developing taste papillae: nerves follow distinctive and spatially restricted pathways. Acta Anat. 160, 139–158 (1997).

    Article  CAS  Google Scholar 

  26. Fritzsch, B., Sarai, P.A., Barbacid, M. & Silos-Santiago, I. Mice with a targeted disruption of the neurotrophin receptor trkB lose their gustatory ganglion cells early but do develop taste buds. Int. J. Dev. Neurosci. 15, 563–576 (1997).

    Article  CAS  Google Scholar 

  27. Jiang, T.X. et al. Integument pattern formation involves genetic and epigenetic controls: feather arrays simulated by digital hormone models. Int. J. Dev. Biol. 48, 117–135 (2004).

    Article  CAS  Google Scholar 

  28. Barlow, L.A. & Northcutt, R.G. Taste buds develop autonomously from endoderm without induction by cephalic neural crest or paraxial mesoderm. Development 124, 949–957 (1997).

    CAS  PubMed  Google Scholar 

  29. Parker, M.A., Bell, M.L. & Barlow, L.A. Cell contact-dependent mechanisms specify taste bud pattern during a critical period early in embryonic development. Dev. Dyn. 230, 630–642 (2004).

    Article  Google Scholar 

  30. Johnson, K.R. et al. P- and E-cadherin are in separate complexes in cells expressing both cadherins. Exp. Cell Res. 207, 252–260 (1993).

    Article  CAS  Google Scholar 

Download references

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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Author notes

  1. Fei Liu and Shoba Thirumangalathu: These authors contributed equally to this work.

Authors and Affiliations

  1. Departments of Dermatology and Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, 19104, Pennsylvania, USA

    Fei Liu, Natalie M Gallant, Seshamma T Reddy, Thomas Andl & Sarah E Millar

  2. Department of Cell and Developmental Biology, University of Colorado Health Sciences Center, Aurora, 80045, Colorado, USA

    Shoba Thirumangalathu & Linda A Barlow

  3. Department of Dermatology, University of Michigan, Ann Arbor, 48109, Michigan, USA

    Steven H Yang & Andrzej A Dlugosz

  4. Department of Pharmacology, Howard Hughes Medical Institute and Institute for Stem Cell and Regenerative Medicine, University of Washington School of Medicine, Seattle, 98195, Washington, USA

    Cristi L Stoick-Cooper & Randall T Moon

  5. Department of Pharmacology, Graduate School of Medicine, Kyoto University, Yoshida-Konoé-cho, Sakyo, 606–8501, Kyoto, Japan

    Makoto M Taketo

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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.

Corresponding authors

Correspondence to Linda A Barlow or Sarah E Millar.

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The authors declare no competing financial interests.

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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