Bioinformatics Database

Tooth development depends on inductive interactions between the dental epithelium and the adjacent mesenchyme. It has been demonstrated that diffusible proteins known as growth factors, such as members of SHH, FGF, BMP, and Wnt families, act as signaling molecules to mediate such interactions (Balic and Thesleff 2015). Tucker et al. (1998) demonstrated that BMP4 activates the expression of Msx1, leading to incisor tooth development. BMP4 inhibited expression of Barx1, which marks presumptive molar teeth, and limits expression to the proximal. Fibroblast growth factor-8 (FGF8; 600483) stimulated Barx1 expression. When BMP4 signaling in early development was inhibited by application of exogenous noggin (NOG) protein, ectopic Barx1 expression resulted in transformation of tooth identity from incisor to molar (Tucker et al., 1998). In mice, FGF8 is expressed in the presumptive dental epithelium prior to the lamina stage and persists there until the bud stage, being responsible for the determination of the tooth-forming site and the initiation of tooth development (Balic and Thesleff 2015). In another study, Liu et al. (2005) found that mice with conditional inactivation of the Bmpr1a gene in the facial primordia developed completely penetrant, bilateral cleft lip/palate with arrested tooth formation. This conditional inactivation of the Bmp4 gene resulted in delayed fusion of the medial nasal process to form the lip, resulting in isolated cleft lip in all mouse embryos. However, cleft lip was only present in 22% of mouse embryos at 14.5 days after conception, indicating spontaneous repair of cleft lip in utero. The findings implicated a BMP4-BMPR1A genetic pathway that functions in lip fusion, and revealed that BMP signaling has distinct roles in lip and palate fusion (Liu et al.,2005).