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

C. A. Ferguson, A. S. Tucker, K. Heikinheimo, Masatoshi Nomura, P. Oh, E. Li, P. T. Sharpe

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

The gene for activin βA 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 βA 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 βA mutant embryos is lost in all tooth germs, including the maxillary molars. These results strongly suggest that other transforming growth factor β 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.

Original languageEnglish
Pages (from-to)4605-4613
Number of pages9
JournalDevelopment
Volume128
Issue number22
Publication statusPublished - Dec 22 2001

Fingerprint

Activins
Tooth
Incisor
Activin Receptors
Tooth Germ
Phenotype
Homeobox Genes
Transforming Growth Factors
Mesoderm
activin receptor type II-A
activin receptor type II-B
Embryonic Structures
Genes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Developmental Biology

Cite this

Ferguson, C. A., Tucker, A. S., Heikinheimo, K., Nomura, M., Oh, P., Li, E., & Sharpe, P. T. (2001). The role of effectors of the activin signalling pathway, activin receptors IIA and IIB, and Smad2, in patterning of tooth development. Development, 128(22), 4605-4613.

The role of effectors of the activin signalling pathway, activin receptors IIA and IIB, and Smad2, in patterning of tooth development. / Ferguson, C. A.; Tucker, A. S.; Heikinheimo, K.; Nomura, Masatoshi; Oh, P.; Li, E.; Sharpe, P. T.

In: Development, Vol. 128, No. 22, 22.12.2001, p. 4605-4613.

Research output: Contribution to journalArticle

Ferguson, CA, Tucker, AS, Heikinheimo, K, Nomura, M, Oh, P, Li, E & Sharpe, PT 2001, 'The role of effectors of the activin signalling pathway, activin receptors IIA and IIB, and Smad2, in patterning of tooth development', Development, vol. 128, no. 22, pp. 4605-4613.
Ferguson CA, Tucker AS, Heikinheimo K, Nomura M, Oh P, Li E et al. The role of effectors of the activin signalling pathway, activin receptors IIA and IIB, and Smad2, in patterning of tooth development. Development. 2001 Dec 22;128(22):4605-4613.
Ferguson, C. A. ; Tucker, A. S. ; Heikinheimo, K. ; Nomura, Masatoshi ; Oh, P. ; Li, E. ; Sharpe, P. T. / The role of effectors of the activin signalling pathway, activin receptors IIA and IIB, and Smad2, in patterning of tooth development. In: Development. 2001 ; Vol. 128, No. 22. pp. 4605-4613.
@article{380a882549a746b68bdbdb3557ba4da7,
title = "The role of effectors of the activin signalling pathway, activin receptors IIA and IIB, and Smad2, in patterning of tooth development",
abstract = "The gene for activin βA 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 βA 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 βA mutant embryos is lost in all tooth germs, including the maxillary molars. These results strongly suggest that other transforming growth factor β 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.",
author = "Ferguson, {C. A.} and Tucker, {A. S.} and K. Heikinheimo and Masatoshi Nomura and P. Oh and E. Li and Sharpe, {P. T.}",
year = "2001",
month = "12",
day = "22",
language = "English",
volume = "128",
pages = "4605--4613",
journal = "Development (Cambridge)",
issn = "0950-1991",
publisher = "Company of Biologists Ltd",
number = "22",

}

TY - JOUR

T1 - The role of effectors of the activin signalling pathway, activin receptors IIA and IIB, and Smad2, in patterning of tooth development

AU - Ferguson, C. A.

AU - Tucker, A. S.

AU - Heikinheimo, K.

AU - Nomura, Masatoshi

AU - Oh, P.

AU - Li, E.

AU - Sharpe, P. T.

PY - 2001/12/22

Y1 - 2001/12/22

N2 - The gene for activin βA 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 βA 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 βA mutant embryos is lost in all tooth germs, including the maxillary molars. These results strongly suggest that other transforming growth factor β 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.

AB - The gene for activin βA 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 βA 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 βA mutant embryos is lost in all tooth germs, including the maxillary molars. These results strongly suggest that other transforming growth factor β 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.

UR - http://www.scopus.com/inward/record.url?scp=0035195082&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035195082&partnerID=8YFLogxK

M3 - Article

C2 - 11714685

AN - SCOPUS:0035195082

VL - 128

SP - 4605

EP - 4613

JO - Development (Cambridge)

JF - Development (Cambridge)

SN - 0950-1991

IS - 22

ER -