title: Runx2 (Cbfa1) inhibits Shh signaling in the lower but not upper molars of mouse embryos and prevents the budding of putative successional teeth.
abstract: Heterozygous mutations in the RUNX2 (CBFA1) gene cause cleidocranial dysplasia, characterized by multiple supernumerary teeth. This suggests that Runx2 inhibits successional tooth formation. However, in Runx2 knockout mice, molar development arrests at the late bud stage, and lower molars are more severely affected than upper ones. We have proposed that compensation by Runx3 may be involved. We compared the molar phenotypes of Runx2/Runx3 double-knockouts with those of Runx2 knockouts, but found no indication of such compensation. Shh and its mediators Ptc1, Ptc2, and Gli1 were down-regulated only in the lower but not the upper molars of Runx2 and Runx2/Runx3 knockouts. Interestingly, in front of the mutant upper molar, a prominent epithelial bud protruded lingually with active Shh signaling. Similar buds were also present in Runx2 heterozygotes, and they may represent the extension of dental lamina for successional teeth. The results suggest that Runx2 prevents the formation of Shh-expressing buds for successional teeth.
authors.affiliation: Developmental Biology Programme, Institute of Biotechnology, Viikki Biocenter, PO Box 56, FIN-00014, University of Helsinki, Finland.
authors.forename: X-P
authors.initials: XP
authors.lastname: Wang
authors.forename: T
authors.initials: T
authors.lastname: Aberg
authors.forename: M J
authors.initials: MJ
authors.lastname: James
authors.forename: D
authors.initials: D
authors.lastname: Levanon
authors.forename: Y
authors.initials: Y
authors.lastname: Groner
authors.forename: I
authors.initials: I
authors.lastname: Thesleff
mesh_terms: D000818:Animals; D050659:Core Binding Factor Alpha 1 Subunit; D050677:Core Binding Factor Alpha 3 Subunit; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D019229:Dentition, Permanent; D005260:Female; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D008334:Mandible / Q000196:embryology / Q000378:metabolism; D008437:Maxilla / Q000196:embryology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008963:Molar / Q000196:embryology*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009805:Odontogenesis / Q000502:physiology*; D014083:Tooth Germ / Q000378:metabolism*; D014094:Tooth, Deciduous / Q000196:embryology / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; D050677:Core Binding Factor Alpha 3 Subunit; D004268:DNA-Binding Proteins; D053823:Hedgehog Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; C493730:Runx3 protein, mouse; C465570:Shh protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors