Implications of the specific localization of YAP signaling on the epithelial patterning of circumvallate papilla

Abstract

Circumvallate papilla (CVP) is a distinctively structured with dome-shaped apex, and the surrounding trench which contains over two hundred taste buds on the lateral walls. Although CVP was extensively studied to determine the regulatory mechanisms during organogenesis, it still remains to be elucidated the principle mechanisms of signaling regulations on morphogenesis including taste buds formation. The key role of Yes-associated protein (YAP) in the regulation of organ size and cell proliferation in vertebrates is well understood, but little is known about the role of this signaling pathway in CVP development. We aimed to determine the putative roles of YAP signaling in the epithelial patterning during CVP morphogenesis. To evaluate the precise localization patterns of YAP and other related signaling molecules, including β-catenin, Ki67, cytokeratins, and PGP9.5, in CVP tissue, histology and immunohistochemistry were employed at E16 and adult mice. Our results suggested that there are specific localization patterns of YAP and Wnt signaling molecules in developing and adult CVP. These concrete localization patterns would provide putative involvements of YAP and Wnt signaling for proper epithelial cell differentiation including the formation and maintenance of taste buds.

This is a preview of subscription content, access via your institution.

We’re sorry, something doesn't seem to be working properly.

Please try refreshing the page. If that doesn't work, please contact support so we can address the problem.

Fig. 1
Fig. 2
Fig. 3

References

  1. Adhikari N, Neupane S, Gwon G-J et al (2017) Grhl3 modulates epithelial structure formation of the circumvallate papilla during mouse development. Histochem Cell Biol 147:5–16. https://doi.org/10.1007/s00418-016-1487-7

    CAS  Article  PubMed  Google Scholar 

  2. Adhikari N, Neupane S, Roh J et al (2018) Immunolocalization patterns of cytokeratins during salivary acinar cell development in mice. J Mol Histol 49:1–15. https://doi.org/10.1007/s10735-017-9742-3

    CAS  Article  PubMed  Google Scholar 

  3. Asano-Miyoshi M, Hamamichi R, Emori Y (2008) Cytokeratin 14 is expressed in immature cells in rat taste buds. J Mol Histol 39:193–199. https://doi.org/10.1007/s10735-007-9151-0

    CAS  Article  PubMed  Google Scholar 

  4. Barlow LA (2015) Progress and renewal in gustation: new insights into taste bud development. Development 142:3620–3629. https://doi.org/10.1242/dev.120394

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  5. Camargo FD, Gokhale S, Johnnidis JB et al (2007) YAP1 increases organ size and expands undifferentiated progenitor cells. Curr Biol 17:2054–2060. https://doi.org/10.1016/j.cub.2007.10.039

    CAS  Article  PubMed  Google Scholar 

  6. Chen Y-A, Lu C-Y, Cheng T-Y et al (2019) WW domain-containing proteins YAP and TAZ in the hippo pathway as key regulators in stemness maintenance, tissue homeostasis, and tumorigenesis. Front Oncol 9:10. https://doi.org/10.3389/fonc.2019.00060

    Article  Google Scholar 

  7. Choi YS, Zhang Y, Xu M et al (2013) Distinct functions for Wnt/β-catenin in hair follicle stem cell proliferation and survival and interfollicular epidermal homeostasis. Cell Stem Cell 13:720–733. https://doi.org/10.1016/j.stem.2013.10.003

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  8. Chou H-C, Chien C-L, Lu K-S (2001) The distribution of PGP9.5, BDNF and NGF in the vallate papilla of adult and developing mice. Anat Embryol (Berl) 204:161–169. https://doi.org/10.1007/s004290100190

    CAS  Article  Google Scholar 

  9. Davis JR, Tapon N (2019) Hippo signalling during development. Development 146:dev167106. https://doi.org/10.1242/dev.167106

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  10. Fevr T, Robine S, Louvard D, Huelsken J (2007) Wnt/β-catenin is essential for intestinal homeostasis and maintenance of intestinal stem cells. Mol Cell Biol 27:7551–7559. https://doi.org/10.1128/MCB.01034-07

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  11. Grigoryan T, Wend P, Klaus A, Birchmeier W (2008) Deciphering the function of canonical Wnt signals in development and disease: conditional loss- and gain-of-function mutations of -catenin in mice. Genes Dev 22:2308–2341. https://doi.org/10.1101/gad.1686208

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  12. Habbig S, Bartram MP, Müller RU et al (2011) NPHP4, a cilia-associated protein, negatively regulates the Hippo pathway. J Cell Biol 193:633–642. https://doi.org/10.1083/jcb.201009069

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  13. Hansen CG, Moroishi T, Guan K-L (2015) YAP and TAZ: a nexus for Hippo signaling and beyond. Trends Cell Biol 25:499–513. https://doi.org/10.1016/j.tcb.2015.05.002

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  14. Heallen T, Zhang M, Wang J et al (2011) Hippo pathway inhibits Wnt signaling to restrain cardiomyocyte proliferation and heart size. Science 332:458–461. https://doi.org/10.1126/science.1199010

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  15. Imajo M, Miyatake K, Iimura A et al (2012) A molecular mechanism that links Hippo signalling to the inhibition of Wnt/β-catenin signalling. EMBO J 31:1109–1122. https://doi.org/10.1038/emboj.2011.487

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  16. Iwasaki S, Aoyagi H, Yoshizawa H (2011) Localization of keratins 13 and 14 in the lingual mucosa of rats during the morphogenesis of circumvallate papillae. Acta Histochem 113:395–401. https://doi.org/10.1016/j.acthis.2010.03.003

    CAS  Article  PubMed  Google Scholar 

  17. Iwasaki S, Yoshizawa H, Aoyagi H (2012) Localization of type III collagen in the lingual mucosa of rats during the morphogenesis of circumvallate papillae. Odontology 100:10–21. https://doi.org/10.1007/s10266-011-0020-7

    CAS  Article  PubMed  Google Scholar 

  18. Iwatsuki K, Liu H-X, Gronder A et al (2007) Wnt signaling interacts with Shh to regulate taste papilla development. Proc Natl Acad Sci 104:2253–2258. https://doi.org/10.1073/pnas.0607399104

    CAS  Article  PubMed  Google Scholar 

  19. Jitpukdeebodintra S, Chai Y, Snead ML (2002) Developmental patterning of the circumvallate papilla. Int J Dev Biol 46:755–763

    CAS  PubMed  Google Scholar 

  20. Jung H-S, Akita K, Kim J-Y (2004) Spacing patterns on tongue surface-gustatory papilla. Int J Dev Biol 48:157–161. https://doi.org/10.1387/ijdb.15272380

    Article  PubMed  Google Scholar 

  21. Kapsimali M, Barlow LA (2013) Developing a sense of taste. Semin Cell Dev Biol 24:200–209. https://doi.org/10.1016/j.semcdb.2012.11.002

    CAS  Article  PubMed  Google Scholar 

  22. Kim M, Jho E (2014) Cross-talk between Wnt/β-catenin and Hippo signaling pathways: a brief review. BMB Rep 47:540–545. https://doi.org/10.5483/BMBRep.2014.47.10.177

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  23. Kim J-Y, Lee M-J, Cho K-W et al (2009) Shh and ROCK1 modulate the dynamic epithelial morphogenesis in circumvallate papilla development. Dev Biol 325:273–280. https://doi.org/10.1016/j.ydbio.2008.10.034

    CAS  Article  PubMed  Google Scholar 

  24. Kim W, Khan SK, Gvozdenovic-Jeremic J et al (2016) Hippo signaling interactions with Wnt/β-catenin and Notch signaling repress liver tumorigenesis. J Clin Invest 127:137–152. https://doi.org/10.1172/JCI88486

    Article  PubMed  PubMed Central  Google Scholar 

  25. Kramer N, Chen G, Ishan M et al (2019) Early taste buds are from Shh + epithelial cells of tongue primordium in distinction from mature taste bud cells which arise from surrounding tissue compartments. Biochem Biophys Res Commun 515:149–155. https://doi.org/10.1016/j.bbrc.2019.05.132

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  26. Lange AW, Sridharan A, Xu Y et al (2015) Hippo/Yap signaling controls epithelial progenitor cell proliferation and differentiation in the embryonic and adult lung. J Mol Cell Biol 7:35–47. https://doi.org/10.1093/jmcb/mju046

    CAS  Article  PubMed  Google Scholar 

  27. Lee M-J, Kim J-Y, Lee S-I et al (2006) Association of Shh and Ptc with keratin localization in the initiation of the formation of circumvallate papilla and von Ebner’s gland. Cell Tissue Res 325:253–261. https://doi.org/10.1007/s00441-006-0160-1

    CAS  Article  PubMed  Google Scholar 

  28. Lian I, Kim J, Okazawa H et al (2010) The role of YAP transcription coactivator in regulating stem cell self-renewal and differentiation. Genes Dev 24:1106–1118. https://doi.org/10.1101/gad.1903310

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  29. Liu F, Thirumangalathu S, Gallant NM et al (2007) Wnt-β-catenin signaling initiates taste papilla development. Nat Genet 39:106–112. https://doi.org/10.1038/ng1932

    CAS  Article  PubMed  Google Scholar 

  30. Mahoney JE, Mori M, Szymaniak AD et al (2014) The Hippo pathway effector yap controls patterning and differentiation of airway epithelial progenitors. Dev Cell 30:137–150. https://doi.org/10.1016/j.devcel.2014.06.003

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  31. Mistretta C, Kumari A (2019) Hedgehog signaling regulates taste organs and oral sensation: distinctive roles in the epithelium, stroma, and innervation. Int J Mol Sci 20:1341. https://doi.org/10.3390/ijms20061341

    CAS  Article  PubMed Central  Google Scholar 

  32. Oakley B, Witt M (2004) Building sensory receptors on the tongue. J Neurocytol 33:631–646. https://doi.org/10.1007/s11068-005-3332-0

    Article  PubMed  Google Scholar 

  33. Pan D (2010) The Hippo signaling pathway in development and cancer. Dev Cell 19:491–505. https://doi.org/10.1016/j.devcel.2010.09.011

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  34. Pan J-X, Xiong L, Zhao K et al (2018) YAP promotes osteogenesis and suppresses adipogenic differentiation by regulating β-catenin signaling. Bone Res 6:18. https://doi.org/10.1038/s41413-018-0018-7

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  35. Panciera T, Azzolin L, Fujimura A et al (2016) Induction of expandable tissue-specific stem/progenitor cells through transient expression of YAP/TAZ. Cell Stem Cell 19:725–737. https://doi.org/10.1016/j.stem.2016.08.009

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  36. Pinto D (2003) Canonical Wnt signals are essential for homeostasis of the intestinal epithelium. Genes Dev 17:1709–1713. https://doi.org/10.1101/gad.267103

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  37. Thirumangalathu S, Barlow LA (2015) Catenin signaling regulates temporally discrete phases of anterior taste bud development. Development 142:4309–4317. https://doi.org/10.1242/dev.121012

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  38. Uchida N, Kanazawa M, Suzuki Y, Takeda M (2003) Expression of BDNF and TrkB in mouse taste buds after denervation and in circumvallate papillae during development. Arch Histol Cytol 66:17–25. https://doi.org/10.1679/aohc.66.17

    CAS  Article  PubMed  Google Scholar 

  39. Varelas X (2014) The Hippo pathway effectors TAZ and YAP in development, homeostasis and disease. Development 141:1614–1626. https://doi.org/10.1242/dev.102376

    CAS  Article  PubMed  Google Scholar 

  40. Wang Y, Yu A, Yu F-X (2017) The Hippo pathway in tissue homeostasis and regeneration. Protein Cell 8:349–359. https://doi.org/10.1007/s13238-017-0371-0

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  41. Yu F-X, Zhao B, Guan K-L (2015) Hippo pathway in organ size control, tissue homeostasis, and cancer. Cell 163:811–828. https://doi.org/10.1016/j.cell.2015.10.044

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  42. Zhang W, Meyfeldt J, Wang H et al (2019) β-Catenin mutations as determinants of hepatoblastoma phenotypes in mice. J Biol Chem 294:17524–17542. https://doi.org/10.1074/jbc.RA119.009979

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  43. Zhang S, Lee J-M, Ashok AA, Jung H-S (2020) Action of actomyosin contraction with Shh modulation drive epithelial folding in the circumvallate papilla. Front Physiol. https://doi.org/10.3389/fphys.2020.00936

    Article  PubMed  PubMed Central  Google Scholar 

  44. Zhao B, Wei X, Li W et al (2007) Inactivation of YAP oncoprotein by the Hippo pathway is involved in cell contact inhibition and tissue growth control. Genes Dev 21:2747–2761. https://doi.org/10.1101/gad.1602907

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  45. Zhao R, Fallon TR, Saladi SV et al (2014) Yap tunes airway epithelial size and architecture by regulating the identity, maintenance, and self-renewal of stem cells. Dev Cell 30:151–165. https://doi.org/10.1016/j.devcel.2014.06.004

    CAS  Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was supported by a grant from the National Research Foundation of Korea (NRF) funded by the Korean government (Grant No. NRF-2019R1I1A3A01062091).

Author information

Affiliations

Authors

Contributions

JYK and TYK contributed to conception, data acquisition, analysis and interpretation, drafted and revised the manuscript. ESL and YPA contributed to the analysis and interpretation of data. EP, SS, and WJS contributed to the analysis and quantification of data. JYK and JKJ contributed to conception, design, analysis and data interpretation and critically revised the manuscript.

Corresponding authors

Correspondence to Jae-Young Kim or Jae-Kwang Jung.

Ethics declarations

Conflict of interest

The authors declare that they have no conflicts of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Kim, JY., Kim, TY., Lee, ES. et al. Implications of the specific localization of YAP signaling on the epithelial patterning of circumvallate papilla. J Mol Histol (2021). https://doi.org/10.1007/s10735-020-09951-z

Download citation

Keywords

  • Differentiation
  • Signaling regulation
  • Pattern formation
  • Taste bud
  • Yes‐associated protein