QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ferguson, C. A. Articles by Sharpe, P. T. Search for Related Content PubMed PubMed Citation Articles by Ferguson, C. A. Articles by Sharpe, P. T.

The role of effectors of the activin signalling pathway, activin receptors IIA and IIB, and Smad2, in patterning of tooth development

Christine A. Ferguson^1,*, Abigail S. Tucker^1,*, Kristiina Heikinheimo², Masatoshi Nomura³, Paul Oh³, En Li³ and Paul T. Sharpe^1,

¹ Department of Craniofacial Development, GKT Dental Institute, Kings College London, Floor 28 Guy’s Hospital, London Bridge, London SE1 9RT, UK
² Department of Oral and Maxillofacial Surgery, Institute of Dentistry, University of Turku, FIN-20520 Turku, Finland
³ Cardiovascular Research Centre, Massachusetts General Hospital, Department of Medicine, Harvard Medical School, Charlestown, MA 02129, USA
^* Present address: MRC Centre for Developmental Neurobiology, 4th Floor, New Hunt’s House, Guy’s Campus, King’s College London, London Bridge, London SE1 1UL, UK

Author for correspondence (e-mail: paul.sharpe{at}kcl.ac.uk)

Accepted August 21, 2001

The gene for activin ßA is expressed in the early odontogenic mesenchyme of all murine teeth but mutant mice show a patterning defect where incisors and mandibular molars fail to develop but maxillary molars develop normally. In order to understand why maxillary molar tooth development can proceed in the absence of activin, we have explored the role of mediators of activin signalling in tooth development. Analysis of tooth development in activin receptor II and Smad2 mutants shows that a similar tooth phenotype to activin ßA mutants can be observed. In addition, we identify a novel downstream target of activin signalling, the Iroquois-related homeobox gene, Irx1, and show that its expression in activin ßA mutant embryos is lost in all tooth germs, including the maxillary molars. These results strongly suggest that other transforming growth factor ß molecules are not stimulating the activin signalling pathway in the absence of activin. This was confirmed by a non-genetic approach using exogenous soluble receptors to inhibit all activin signalling in tooth development, which reproduced the genetic phenotypes. Activin, thus, has an essential role in early development of incisor and mandibular molar teeth but this pathway is not required for development of maxillary molars.

Key words: Activin, Activin receptors, Smad2, Irx1, Tooth development, Mouse

This article has been cited by other articles:

				K. L. Bennett, M. Karpenko, M.-t. Lin, R. Claus, K. Arab, G. Dyckhoff, P. Plinkert, E. Herpel, D. Smiraglia, and C. Plass Frequently Methylated Tumor Suppressor Genes in Head and Neck Squamous Cell Carcinoma Cancer Res., June 15, 2008; 68(12): 4494 - 4499. [Abstract] [Full Text] [PDF]

				A.R. Vieira Oral Clefts and Syndromic Forms of Tooth Agenesis as Models for Genetics of Isolated Tooth Agenesis J. Dent. Res., March 1, 2003; 82(3): 162 - 165. [Abstract] [Full Text] [PDF]

				S. P. Oh, C.-Y. Yeo, Y. Lee, H. Schrewe, M. Whitman, and E. Li Activin type IIA and IIB receptors mediate Gdf11 signaling in axial vertebral patterning Genes & Dev., November 1, 2002; 16(21): 2749 - 2754. [Abstract] [Full Text] [PDF]