| Pitx2, a paired-related homeobox transcription factor, is the mutated gene in Rieger's syndrome. Tooth morphogenesis is arrested at very early stage in Pitx2 mutant mouse embryo. Recent evidence suggests that Pitx2 is a target of the canonical Wnt/beta-catenin signaling pathway in pituitary and cardiac development. Here I show that pitx2 functions through Wnt/beta-catenin pathway to regulate tooth development. In the Pitx2cre; beta-cateninflox-/- conditional deletion mutant, tooth morphogenesis is defective, similar to the Pitx2 hypomorphic mutant. Marker analysis and immunohistochemistry results confirmed the defects. The expression pattern of Axin2, a reporter gene of the canonical Wnt pathway, was deficient in Pitx2 hypomorphic mutant mice, similar to that in the Pitx2cre; beta-cateninflox-/- mutant. Both Pitx2 hypomorph and Pitx2cre; beta-cateninflox-/- mutant embryos showed expression defect in CycliD2, a cell cycle specific gene, which was suggestive of a proliferation defect. The stabilized beta-catenin allele can rescue the Pitx2 mutant tooth phenotype. These data suggest that the function of pitx2 in tooth development is dependent on the canonical Wnt pathway.;The regulatory mechanisms underlying craniofacial muscle development are poorly understood. Previous evidence suggests that the genetic programs controlling craniofacial muscle formation are different from those controlling trunk myogenesis. Here we investigate the role of Pitx2 homeobox gene in craniofacial muscle development. In Pitx2 null embryos, craniofacial muscle failed to form. The absence of both MyoD, a muscle specification marker and Myogenin, a muscle differentiation marker expression, indicates the failure of determination and differentiation in first branchial muscle. Fate mapping results demonstrate that the migration of muscle precursor cells into first branchial arch is deficient in the Pitx2 null mutant. Mesoderm specific ablation of Pitx2 leads to the myogenic failure, suggesting that Pitx2 plays a cell autonomous role in craniofacial myogenesis. Our data established that Pitx2 is required for the craniofacial muscle development. |
