Skip to main content

Advertisement

Log in

Sonic hedgehog signaling is critical for cytodifferentiation and cusp formation in developing mouse molars

  • Original paper
  • Published:
Journal of Molecular Histology Aims and scope Submit manuscript

Abstract

The present study was designed to investigate the direct role of Shh molecule on cytodifferentiation and cusp formation. Affi-gel blue beads soaked in exogenous Shh-N, Shh antibody or BSA control protein were implanted between the epithelium and mesenchyme of isolated molar germs at the cap stage. The recombinants were grafted for culture under the kidney capsules respectively. In compared to the control, additional Shh-N protein could not enhance the ameloblasts and odontoblasts differentiation of the explanted tooth germs. While, application of Shh antibody retarded these events. After 4 weeks of subrenal culture, the teeth dissected from the explants treated with Shh-N were multicuspid. Most of the teeth harvested from the Shh antibody group were small and single irregularly shaped cusp was visible. The main cusp height in this group was reduced. The results indicated Shh signaling pathway is critical for odontoblast and ameloblast differentiation and patterns cusp formation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Blanc I, Bach A, Robert B (2002) Unusual pattern of Sonic hedgehog expression in the polydactylous mouse mutant Hemimelic extra-toes. Int J Dev Biol 46:969–974

    PubMed  CAS  Google Scholar 

  • Cobourne MT, Hardcastle Z, Sharpe PT (2001) Sonic hedgehog regulates epithelial proliferation and cell survival in the developing tooth germ. J Dent Res 80:1974–1979

    Article  PubMed  CAS  Google Scholar 

  • Cobourne MT, Miletich I, Sharpe PT (2004) Restriction of sonic hedgehog signaling during early tooth development. Development 131:2875–2885

    Article  PubMed  CAS  Google Scholar 

  • Coin R, Kieffer S, Lesot H, Vonesch JL, Ruch JV (2000) Inhibition of apoptosis in the primary enamel knot does not affect specific tooth crown morphogenesis in the mouse. Int J Dev Biol 44:389–396

    PubMed  CAS  Google Scholar 

  • Dassule H, Lewis P, Bei M, Maas R, Mcmahon AP (2000) Sonic hedgehog regulates growth and morphogenesis of the tooth. Development 127:4775–4785

    PubMed  CAS  Google Scholar 

  • Gritli-Linde A, Lewis P, McMahon AP, Linde A (2001) The whereabouts of a morphogen: direct evidence for short- and graded long-range activity of hedgehog signaling peptides. Dev Biol 236:364–386

    Article  PubMed  CAS  Google Scholar 

  • Gritli-Linde A, Bei M, Maas R, Zhang XM, Linde A, McMahon AP (2002) Shh signaling within the dental epithelium is necessary for cell proliferation, growth and polarization. Development 129:5323–5337

    Article  PubMed  CAS  Google Scholar 

  • Hammerschmidt M, Brook A, McMahon AP (1997) The world according to hedgehog. Trends Genet 13:14–21

    Article  PubMed  CAS  Google Scholar 

  • Hardcastle Z, Mo R, Hui CC, Sharpe PT (1998) The Shh signaling pathway in tooth development: defects in Gli2 and Gli3 mutants. Development 125:2803–2811

    PubMed  CAS  Google Scholar 

  • Hardcastle Z, Hui CC, Sharpe PT (1999) The Shh signaling pathway in early tooth development. Cell Mol Biol 45:567–578

    PubMed  CAS  Google Scholar 

  • Iseki S, Araga A, Ohuchi H, Nohno T, Yoshioka H, Hayashi F, Noji S (1996) Sonic hedgehog is expressed in epithelial cells during development of whisker, hair, and tooth. Biochem Biophys Res Commun 218:688–693

    Article  PubMed  CAS  Google Scholar 

  • Jernvall J, Kettunen P, Karavanova I, Martin LB, Thesleff I (1994) Evidence for the role of the enamel knot as a control center in mammalian tooth cusp formation: non-dividing cells express growth stimulating FGF-4 gene. Int J Dev Biol 38:463–469

    PubMed  CAS  Google Scholar 

  • Koyama E, Yamaai T, Iseki S, Ohuchi H, Nohno T, Yoshioka H, Hayashi Y, Leatherman JL, Golden EB, Noji S, Pacifici M (1996) Polarizing activity, Sonic hedgehog, and tooth development in embryonic and postnatal mouse. Dev Dyn 206:59–72

    Article  PubMed  CAS  Google Scholar 

  • Lesot H (2000) Odontoblast differentiation and tooth morphogenesis. J Dent Res 79:1640–1644

    PubMed  CAS  Google Scholar 

  • Martin A, Unda FJ, Begue-kim C, Ruch JV, Arechaga J (1998) Effects of aFGF, bFGF, TGFbeta1 and IGF-I on odontoblast differentiation in vitro. Eur J Oral Sci 106:117–121

    PubMed  CAS  Google Scholar 

  • Mcmahon AP (2000) More Surprises in the Hedgehog signaling pathway. Cell 100:185–188

    Article  PubMed  CAS  Google Scholar 

  • Mitsiadis T, Hirsinger E, Lendahi U, Goridis C (1998) Delta-Notch signaling in odontogenesis: correlation with cytodifferentiation and evidence for feedback regulation. Dev Biol 204:420–431

    Article  PubMed  CAS  Google Scholar 

  • Ohazama A, Courtney JM, Tucker AS, Naito A, Tanaka S, Inoue J, Sharpe PT (2004) Traf6 is essential for murine tooth cusp morphogenesis. Dev Dyn 229:131–135

    Article  PubMed  CAS  Google Scholar 

  • Peterkova R, Peterka M, Viriot L, Lesot H (2000) Dentition development and budding morphogenesis. J Craniofac Genet Dev Biol 20:158–172

    PubMed  CAS  Google Scholar 

  • Sarkar L, Sharpe PT (2000) Inhibition of Wnt signaling by exogenous Mfrzb1 protein affects molar tooth size. J Dent Res 79:920–925

    PubMed  CAS  Google Scholar 

  • Sarkar L, Cobourne M, Naylor S, Smalley M, Dale T, Sharpe PT (2000) Wnt/Shh interactions regulate ectodermal boundary formation during mammalian tooth development. Proc Natl Acad Sci USA 97:4520–4524

    Article  PubMed  CAS  Google Scholar 

  • Thesleff I (2003) Epithelial-mesenchymal signaling regulating tooth morphogenesis. J Cell Sci 116:1647–1648

    Article  PubMed  CAS  Google Scholar 

  • Thesleff I, Vaahtokari A, Partanen AM (1995) Regulation of organogenesis. Common molecular mechanisms regulating the development of teeth and other organs. Int J Dev Biol 39:35–50

    PubMed  CAS  Google Scholar 

  • Tucker AS, Sharpe PT (2004) The cutting-edge of mammalian development: How the embryo makes teeth. Nat Rev Genet 5:499 –508

    Article  PubMed  CAS  Google Scholar 

  • Tucker AS, Headon DJ, Courtney JM, Overbeek P, Sharpe PT (2004) The activation level of the TNF family receptor, Edar, determines cusp number and tooth number during tooth development. Dev Biol 268:185–194

    Article  PubMed  CAS  Google Scholar 

  • Vaahtokari A, Abert T, Jernvall J, Keranen S, Thesleff I (1996) The enamel knot as a signaling center in the developing mouse tooth. Mech Dev 54:39–43

    Article  PubMed  CAS  Google Scholar 

  • Zeichner-David M, Diekwisch T, Fincham A, Lau E, Macdougall M, Moradian-Oidak J, Simmer J, Snead M, Slavkin HC (1995) Control of ameloblast differentiation. Int J Dev Biol 39:69–92

    PubMed  CAS  Google Scholar 

  • Zhang YD, Zhao X, Hu Y, Amand TSt, Zhang M, Ramanurthy R, Qiu M, Chen YP (1999) Msx1 is required for the Shh-N of Patched by Sonic hedgehog in the mammalian tooth germ. Dev Dyn 215:45–53

    Article  PubMed  CAS  Google Scholar 

  • Zhang YD, Wang S, Song YQ, Han J, Chai Y, Chen YP (2003) Timing of odontogenic neural crest cell migration and tooth-forming capability in mice. Dev Dyn 226:713–718

    Article  PubMed  Google Scholar 

  • Zhang YD, Chen Z, Song YQ, Liu C, Chen YP (2005) Making a tooth: growth factors, transcription factors, and stem cells. Cell Res 15:301–316

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

We thank Prof. Andrew McMahon (Harvard University, USA) for providing Shh plasmid and Prof. Yi-Ping Chen (Ohio State University, USA) for advice. This research was supported by the grants from National Natural Science Foundation of China (30171011) to Prof. Zhi Chen and the grants from Fujian Provincial Department of Science and Technology, China (No. 2002I006, CO320003) to Prof. Yan-Ding Zhang.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Yan-Ding Zhang or Zhi Chen.

Additional information

Lu Zhang and Fang Hua contribute equally.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhang, L., Hua, F., Yuan, GH. et al. Sonic hedgehog signaling is critical for cytodifferentiation and cusp formation in developing mouse molars. J Mol Hist 39, 87–94 (2008). https://doi.org/10.1007/s10735-007-9132-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10735-007-9132-3

Keywords

Navigation