Alteration in the expression of bone morphogenetic protein-2,3,4,5 mRNA during pathogenesis of cleft palate in BALB/c mice.

To identify the function of these bone morphogenetic proteins (BMP) during pathogenesis of cleft palate, an experimental model was established in BALB/c mice. Cleft palate was induced by exposure to retinoic acid on embryonic day (E)12. The expression of BMP-2,3,4,5 mRNA in normal and abnormal embryonic palatal shelves was then examined from E13 to E16 by in situ hybridization. The results showed that BMP-4 mRNA was expressed strongly and uniformly in normal epithelial cells and dispersed mesenchymal cells on E13. BMP-2,5 mRNA expression appeared only in dispersed mesenchymal cells. With the development of shelves, the staining density of BMP-2,4,5 decreased gradually in mesenchymal cells outside of the condensation and increased inside the condensation. After shelves had fused on E16, no positive signals for BMP-2,4,5 were detected in dispersed mesenchymal cells, but their expression persisted in the condensation. Exposure to retinoic acid delayed the formation of the condensation and decreased BMP-2,4,5 mRNA dramatically in mesenchyme from E13 to E15. BMP-3 mRNA expression were almost negative in either control or retinoic acid-treated groups during all stages. It was concluded that spatial and temporal expression of BMP-2,4,5 was required during normal palatogenesis, and that a deficiency of their mRNA expression may contribute to the pathogenesis of cleft palate.