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First published online 11 February 2009
doi: 10.1242/dev.027979

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

¹ Department of Craniofacial Development, Dental Institute, King's College London, London SE1 9RT, UK.
² Department of Cell Biology, University of Alabama at Birmingham, Birmingham, AL 35294-0005, USA.
³ Department of Craniofacial Development and Orthodontics, Dental Institute, King's College London, UK.
⁴ Department of Embryology, Carnegie Institution of Washington 3520 San Martin Drive, Baltimore, MD 21218, USA.
⁵ Department of Teratology, Institute of Experimental Medicine, Academy of Sciences of the CR, Prague, Czech Republic.
⁶ INSERM UMR977, Dental School, Strasbourg University, Strasbourg, France.

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

Accepted 21 January 2009

SUMMARY

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.

Key words: Intraflagellar transport, Cilia, Shh, Supernumerary tooth, Tooth development, Tooth number, Orpk, Tg737, Gas1, Epithelium, Mesenchyme, Mouse

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