Pitx2 function is mandatory for tooth development

Rieger syndrome is an autosomal dominant disorder with malformations of the anterior chamber of the eye, umbilical anomalies, and hypodontia. The maxillary primary and permanent incisors and second premolars are the most commonly missing. Peg-shaped incisors have also been reported. Hypodontia in the anterior region of the maxilla results in underdevelopment of the premaxillary area (Gorlin et al, 1990). Rieger syndrome has proven to be genetically heterogenous. Mutations has been found in a homeobox transcription factor gene, PITX2 in 4q25-q26 (Semina et al, 1996). Another locus for Rieger syndrome has been identified on 13q14 by linkage analysis (Phillips et al, 1996), but the gene has not yet been found. PITX2 is a homeobox gene, related to Drosophila bicoid class. The analysis of expression of the mouse homologue indicated that it is expressed in the mandibular and maxillary epithelium during early tooth morphogenesis. The mouse gene was also cloned independently by another group and called Otlx2. It was shown that the expression in the presumptive tooth epithelium starts very early, already at E8.5 and that the expression persists in the dental epithelium throughout tooth morphogenesis (Mucchielli et al, 1996). It is possible that Pitx2 is involved in the initiation of tooth formation. It appears to be associated with epithelial-mesenchymal interactions, and it was shown that the expression of Pitx2 can be induced in non-dental, Pitx2 negative epithelium by dental mesenchyme. In Pitx2 null mutant mice tooth development is arrested at bud stage while heterozygotes are normal.

Text partially adapted from Sirpa Arte: Phenotypic and genotypic features of familial hypodontia. Dissertation, Institute of Dentistry, University of Helsinki, Finland, 2001.


Jackson Mouse Genome Database Transgene Database OMIM

Text last edited 31.12.2000 by P.N. , page last created 10.12.2004 by P.N.