|
|
|
|
|
|
|
||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | ||||
First published online 19 May 2004
doi: 10.1242/dev.01163
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Craniofacial Development and Orthodontics, GKT Dental Institute,
King's College London, Floor 28, Guy's Hospital, London SE1 9RT, UK
2 Department of Craniofacial Development, GKT Dental Institute, King's College
London, Floor 28, Guy's Hospital, London SE1 9RT, UK
* Author for correspondence (e-mail: paul.sharpe{at}kcl.ac.uk)
Accepted 10 March 2004
The signalling peptide encoded by the sonic hedgehog gene is restricted to localised thickenings of oral epithelium, which mark the first morphological evidence of tooth development, and is known to play a crucial role during the initiation of odontogenesis. We show that at these stages in the murine mandibular arch in the absence of epithelium, the Shh targets Ptc1 and Gli1 are upregulated in diastema mesenchyme, an edentulous region between the sites of molar and incisor tooth formation. This ectopic expression is not associated with Shh transcription but with Shh protein, undetectable in the presence of epithelium. These findings suggest that, in diastema mesenchyme, restriction of Shh activity is dependent upon the overlying epithelium. This inhibitory activity was demonstrated by the ability of transplanted diastema epithelium to downregulate Ptc1 in tooth explants, and for isolated diastema mesenchyme to express Ptc1. A candidate inhibitor in diastema mesenchyme is the glycosylphosphatidylinositol-linked membrane glycoprotein Gas1. Gas1 is normally expressed throughout mandibular arch mesenchyme; however, in the absence of epithelium this expression was downregulated specifically in the diastema where ectopic Shh protein was identified. Although Shh signalling has no effect upon Gas1 expression in mandibular arch mesenchyme, overexpression of Gas1 results in downregulation of ectopic Ptc1. Therefore, control of the position of tooth initiation in the mandibular arch involves a combination of Shh signalling at sites where teeth are required and antagonism in regions destined to remain edentulous.
Key words: Shh, Gas1, Tooth development, Diastema, Mandibular arch
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati 
Twitter What's this?
This article has been cited by other articles:
|
|
 |
|
  T. Sagai, T. Amano, M. Tamura, Y. Mizushina, K. Sumiyama, and T. Shiroishi A cluster of three long-range enhancers directs regional Shh expression in the epithelial linings Development, May 15, 2009; 136(10): 1665 - 1674. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. M Smith, G. J Fraser, N. Chaplin, C. Hobbs, and A. Graham Reiterative pattern of sonic hedgehog expression in the catshark dentition reveals a phylogenetic template for jawed vertebrates Proc R Soc B, April 7, 2009; 276(1660): 1225 - 1233. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Ohazama, C. J. Haycraft, M. Seppala, J. Blackburn, S. Ghafoor, M. Cobourne, D. C. Martinelli, C.-M. Fan, R. Peterkova, H. Lesot, et al. Primary cilia regulate Shh activity in the control of molar tooth number Development, March 15, 2009; 136(6): 897 - 903. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. M Smith, M. Okabe, and J. Joss Spatial and temporal pattern for the dentition in the Australian lungfish revealed with sonic hedgehog expression profile Proc R Soc B, February 22, 2009; 276(1657): 623 - 631. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. M. Munne, M. Tummers, E. Jarvinen, I. Thesleff, and J. Jernvall Tinkering with the inductive mesenchyme: Sostdc1 uncovers the role of dental mesenchyme in limiting tooth induction Development, February 1, 2009; 136(3): 393 - 402. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Gobeil, X. Zhu, C. J. Doillon, and M. R. Green A genome-wide shRNA screen identifies GAS1 as a novel melanoma metastasis suppressor gene Genes & Dev., November 1, 2008; 22(21): 2932 - 2940. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Varjosalo and J. Taipale Hedgehog: functions and mechanisms Genes & Dev., September 15, 2008; 22(18): 2454 - 2472. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G.H. Yuan, L. Zhang, Y.D. Zhang, M.W. Fan, Z. Bian, and Z. Chen Mesenchyme is Responsible for Tooth Suppression in the Mouse Lower Diastema Journal of Dental Research, April 1, 2008; 87(4): 386 - 390. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. C. Martinelli and C.-M. Fan Gas1 extends the range of Hedgehog action by facilitating its signaling Genes & Dev., May 15, 2007; 21(10): 1231 - 1243. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. L. Allen, T. Tenzen, and A. P. McMahon The Hedgehog-binding proteins Gas1 and Cdo cooperate to positively regulate Shh signaling during mouse development Genes & Dev., May 15, 2007; 21(10): 1244 - 1257. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X.-M. Gu, H.-S. Zhao, L.-S. Sun, and T.-J. Li PTCH Mutations in Sporadic and Gorlin-syndrome-related Odontogenic Keratocysts Journal of Dental Research, September 1, 2006; 85(9): 859 - 863. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. W. Stock, W. R. Jackman, and J. Trapani Developmental genetic mechanisms of evolutionary tooth loss in cypriniform fishes Development, August 15, 2006; 133(16): 3127 - 3137. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X.-P. Wang, T. Aberg, M.J. James, D. Levanon, Y. Groner, and I. Thesleff Runx2 (Cbfa1) Inhibits Shh Signaling in the Lower but not Upper Molars of Mouse Embryos and Prevents the Budding of Putative Successional Teeth Journal of Dental Research, February 1, 2005; 84(2): 138 - 143. [Abstract] [Full Text] [PDF]
|
|
