The Role of BCoR During Murine Tooth Development

Introduction: BCoR (Bcl-6 interacting corepressor) was originally identified as a transcriptional corepressor of the oncoprotein Bcl-6 and mutations in BCoR have been described to cause human Oculofaciocardiodental Syndrome (OFCD). This syndrome is characterized by microphthalmia, dysmorphic facial features, congenital heart disease and canine teeth with unusual long roots (canine radiculomegaly).

Objectives: To investigate the role of BCoR in murine tooth development.

Methods: Mandible primordia of CD1 mice ranging from E11.5-P20 were used. Expression patterns of BCoR and its possible partners were investigated by radioactive and wholemount in situ hybridization. To study the regulation of BCoR, mouse tooth germs were dissected and cultured in Trowell-type organ cultures. After culture, the explants were analyzed using wholemount in situ hybridization.

Results: During early molar development, BCoR is expressed in both epithelial and mesenchymal compartments with a marked upregulation in the condensed dental mesenchyme at the bud stage. At later stages BCoR is co-expressed in root odontoblasts with Bcl-6. We further analyzed tooth development in Bcl-6 knockout mice and also investigated expression of BCoR in NFI-C-/- molars lacking roots. During incisor development, BCoR is expressed ubiquitously at E16.5 and its expression becomes more specific from E18.5 onwards. At E18.5 BCoR is strongly expressed in apical dental mesenchyme. Using an inhibitor of FGF (Fibroblast Growth Factor) signalling, SU5402, we have found that the expression of BCoR is upregulated in incisor dental mesenchyme but not in molar odontoblasts.

Conclusion: Expression patterns of BCoR and Bcl-6 suggest that BCoR may be important for early tooth development. During these early stages BCoR would interact with another partner than Bcl-6. During late stages of root development, BCoR possibly interacts with Bcl-6 to regulate root formation through root dentinogenesis. The data also suggest that FGF signalling may act upstream of BCoR by repressing BCoR mesenchymal expression in mouse incisor development.