Function analysis of mesenchymal Bcor in tooth development by using RNA interference

Abstract

Teeth, an excellent model for studying organogenesis, develop from a series of epithelial-mesenchymal interactions that are mediated by a complex molecular network. Bcor (BCL-6 interacting corepressor) has recently been discovered, but little is known about its function in tooth development. Mutations in BCOR affect humans with oculofaciocardiodental syndrome, which is an X-linked dominant disorder with presumed male lethality and which comprises microphthalmia, congenital cataracts, radiculomegaly, and cardiac and digital abnormalities. In this study, the Bcor expression pattern has been intensively investigated during mouse molar development. Bcor is expressed in both dental epithelium and the mesenchyme at E11.5. To understand the function of Bcor, knockdown of Bcor has been examined by using lentivirus-mediated RNA interference. Silencing of Bcor expression in dental mesenchymal cells at E14.5 causes dentinogenesis defects and retardation of tooth root development. Thus, our results suggest that Bcor expressed in the mesenchyme plays crucial roles during early tooth development. The function of Bcor expressed in the epithelium remains to be elucidated.

Genome-wide Association Studies of Pit-and-Fissure- and Smooth-surface Caries in Permanent Dentition

“…Further, the osteo-dentinogenic potential was found to be increased in mesenchymal stem cells isolated from an OFCD patient with a BCOR mutation (Fan et al, 2009). A study exploring the role of Bcor in tooth development of mice found that silenced Bcor expression by RNA interference in dental tissues caused dentinogenesis defects and retardation of tooth root development (Cai et al, 2010). No direct role of BCOR in dental caries has been established.…”

BCOR mutations and unstoppable root growth: a commentary on oculofaciocardiodental syndrome: novel BCOR mutations and expression in dental cells

“…Bcor is highly expressed in the tongue during early development but, interestingly, patients with BCOR mutations have never been reported to have tongue anomalies. 5 Besides radiculomegaly and hyperdontia, all other defects in OFCD syndrome appear to be 'deficiency' defects such as cardiac septal defects, hypodontia and cleft palate. Continuous root growth and hyperdontia appear to be the opposite.…”

“…4 It is not surprising that BCOR mutations are associated with dental anomalies, including hypodontia, hyperdontia and radiculomegaly since Bcor is expressed in both dental epithelium and the mesenchyme during the early stages of tooth development. 5 Knockdown experiments of Bcor expression in dental mesenchymal cells using the lentivirusmediated RNA interference approach have demonstrated that during early tooth development Bcor in mesenchyme has crucial roles in cellular events, such as apoptosis and cellular differentiation. 5,6 It is important to note that BCL-6 is not expressed in tooth primordium in early embryogenesis.…”

“…5 Knockdown experiments of Bcor expression in dental mesenchymal cells using the lentivirusmediated RNA interference approach have demonstrated that during early tooth development Bcor in mesenchyme has crucial roles in cellular events, such as apoptosis and cellular differentiation. 5,6 It is important to note that BCL-6 is not expressed in tooth primordium in early embryogenesis. 7 This implies that the role of Bcor in tooth development is BCL-6-independent 5,8 and the dental phenotypes found in patients affected with BCOR mutations are not associated with BCL-6.…”

“…This pattern of Bcor expression indicates the crucial role of Bcor in root development. 5 What controls the length of the root is still a mystery. In the normal situation the stem cell niche disappears, HERS invaginates and apical root closure commences.…”