Primary cilia regulate Shh activity in the control of molar tooth number

Atsushi Ohazama; Courtney J. Haycraft; Maisa Seppala; James Blackburn; Sarah Ghafoor; Martyn Cobourne; David C. Martinelli; Chen-Ming Fan; Renata Peterkova; Herve Lesot; Bradley K. Yoder; Paul T. Sharpe

doi:10.1242/dev.027979

Primary cilia regulate Shh activity in the control of molar tooth number

Atsushi Ohazama, Courtney J. Haycraft, Maisa Seppala, James Blackburn, Sarah Ghafoor, Martyn Cobourne, David C. Martinelli, Chen-Ming Fan, Renata Peterkova, Herve Lesot, Bradley K. Yoder, Paul T. Sharpe

Centre for Craniofacial & Regenerative Biology

Research output: Contribution to journal › Article › peer-review

114 Citations (Scopus)

Abstract

Primary cilia mediate Hh signalling and mutations in their protein components affect Hh activity. We show that in mice mutant for a cilia intraflagellar transport (IFT) protein, IFT88/polaris, Shh activity is increased in the toothless diastema mesenchyme of the embryonic jaw primordia. This results in the formation of ectopic teeth in the diastema, mesial to the first molars. This phenotype is specific to loss of polaris activity in the mesenchyme since loss of Polaris in the epithelium has no detrimental affect on tooth development. To further confirm that upregulation of Shh activity is responsible for the ectopic tooth formation, we analysed mice mutant for Gas1, a Shh protein antagonist in diastema mesenchyme. Gas1 mutants also had ectopic diastema teeth and accompanying increased Shh activity. In this context, therefore, primary cilia exert a specific negative regulatory effect on Shh activity that functions to repress tooth formation and thus determine tooth number. Strikingly, the ectopic teeth adopt a size and shape characteristic of premolars, a tooth type that was lost in mice around 50-100 million years ago.

Original language	English
Pages (from-to)	897 - 903
Number of pages	7
Journal	Development (Cambridge): for advances in developmental biology and stem cells
Volume	136
Issue number	6
Early online date	11 Feb 2009
DOIs	https://doi.org/10.1242/dev.027979
Publication status	Published - 15 Mar 2009

Access to Document

10.1242/dev.027979

Cite this

Ohazama, A., Haycraft, C. J., Seppala, M., Blackburn, J., Ghafoor, S., Cobourne, M., Martinelli, D. C., Fan, C.-M., Peterkova, R., Lesot, H., Yoder, B. K., & Sharpe, P. T. (2009). Primary cilia regulate Shh activity in the control of molar tooth number. Development (Cambridge): for advances in developmental biology and stem cells, 136(6), 897 - 903. https://doi.org/10.1242/dev.027979

@article{ba7253cda9cf438a8804c8421ae4f432,

title = "Primary cilia regulate Shh activity in the control of molar tooth number",

abstract = "Primary cilia mediate Hh signalling and mutations in their protein components affect Hh activity. We show that in mice mutant for a cilia intraflagellar transport (IFT) protein, IFT88/polaris, Shh activity is increased in the toothless diastema mesenchyme of the embryonic jaw primordia. This results in the formation of ectopic teeth in the diastema, mesial to the first molars. This phenotype is specific to loss of polaris activity in the mesenchyme since loss of Polaris in the epithelium has no detrimental affect on tooth development. To further confirm that upregulation of Shh activity is responsible for the ectopic tooth formation, we analysed mice mutant for Gas1, a Shh protein antagonist in diastema mesenchyme. Gas1 mutants also had ectopic diastema teeth and accompanying increased Shh activity. In this context, therefore, primary cilia exert a specific negative regulatory effect on Shh activity that functions to repress tooth formation and thus determine tooth number. Strikingly, the ectopic teeth adopt a size and shape characteristic of premolars, a tooth type that was lost in mice around 50-100 million years ago.",

author = "Atsushi Ohazama and Haycraft, {Courtney J.} and Maisa Seppala and James Blackburn and Sarah Ghafoor and Martyn Cobourne and Martinelli, {David C.} and Chen-Ming Fan and Renata Peterkova and Herve Lesot and Yoder, {Bradley K.} and Sharpe, {Paul T.}",

year = "2009",

month = mar,

day = "15",

doi = "10.1242/dev.027979",

language = "English",

volume = "136",

pages = "897 -- 903",

journal = "Development (Cambridge): for advances in developmental biology and stem cells",

issn = "1477-9129",

publisher = "Company of Biologists Ltd",

number = "6",

}

Ohazama, A, Haycraft, CJ, Seppala, M, Blackburn, J, Ghafoor, S, Cobourne, M, Martinelli, DC, Fan, C-M, Peterkova, R, Lesot, H, Yoder, BK & Sharpe, PT 2009, 'Primary cilia regulate Shh activity in the control of molar tooth number', Development (Cambridge): for advances in developmental biology and stem cells, vol. 136, no. 6, pp. 897 - 903. https://doi.org/10.1242/dev.027979

TY - JOUR

T1 - Primary cilia regulate Shh activity in the control of molar tooth number

AU - Ohazama, Atsushi

AU - Haycraft, Courtney J.

AU - Seppala, Maisa

AU - Blackburn, James

AU - Ghafoor, Sarah

AU - Cobourne, Martyn

AU - Martinelli, David C.

AU - Fan, Chen-Ming

AU - Peterkova, Renata

AU - Lesot, Herve

AU - Yoder, Bradley K.

AU - Sharpe, Paul T.

PY - 2009/3/15

Y1 - 2009/3/15

N2 - Primary cilia mediate Hh signalling and mutations in their protein components affect Hh activity. We show that in mice mutant for a cilia intraflagellar transport (IFT) protein, IFT88/polaris, Shh activity is increased in the toothless diastema mesenchyme of the embryonic jaw primordia. This results in the formation of ectopic teeth in the diastema, mesial to the first molars. This phenotype is specific to loss of polaris activity in the mesenchyme since loss of Polaris in the epithelium has no detrimental affect on tooth development. To further confirm that upregulation of Shh activity is responsible for the ectopic tooth formation, we analysed mice mutant for Gas1, a Shh protein antagonist in diastema mesenchyme. Gas1 mutants also had ectopic diastema teeth and accompanying increased Shh activity. In this context, therefore, primary cilia exert a specific negative regulatory effect on Shh activity that functions to repress tooth formation and thus determine tooth number. Strikingly, the ectopic teeth adopt a size and shape characteristic of premolars, a tooth type that was lost in mice around 50-100 million years ago.

AB - Primary cilia mediate Hh signalling and mutations in their protein components affect Hh activity. We show that in mice mutant for a cilia intraflagellar transport (IFT) protein, IFT88/polaris, Shh activity is increased in the toothless diastema mesenchyme of the embryonic jaw primordia. This results in the formation of ectopic teeth in the diastema, mesial to the first molars. This phenotype is specific to loss of polaris activity in the mesenchyme since loss of Polaris in the epithelium has no detrimental affect on tooth development. To further confirm that upregulation of Shh activity is responsible for the ectopic tooth formation, we analysed mice mutant for Gas1, a Shh protein antagonist in diastema mesenchyme. Gas1 mutants also had ectopic diastema teeth and accompanying increased Shh activity. In this context, therefore, primary cilia exert a specific negative regulatory effect on Shh activity that functions to repress tooth formation and thus determine tooth number. Strikingly, the ectopic teeth adopt a size and shape characteristic of premolars, a tooth type that was lost in mice around 50-100 million years ago.

U2 - 10.1242/dev.027979

DO - 10.1242/dev.027979

M3 - Article

SN - 1477-9129

VL - 136

SP - 897

EP - 903

JO - Development (Cambridge): for advances in developmental biology and stem cells

JF - Development (Cambridge): for advances in developmental biology and stem cells

IS - 6

ER -

Primary cilia regulate Shh activity in the control of molar tooth number

Abstract

Access to Document

Fingerprint

Cite this