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 embry onic palatal shelves was then examined from E13 to E16 by in situ hybridiza tion. The results showed that BMP-4 mRNA was expressed strongly and uniform ly in normal epithelial cells and dispersed mesenchymal cells on E13. BMP-2 ,5 mRNA expression appeared only in dispersed mesenchymal cells. With the d evelopment of shelves, the staining density of BMP-2,4,5 decreased graduall y 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 pe rsisted in the condensation. Exposure to retinoic acid delayed the formatio n of the condensation and decreased BMP-2,4,5 mRNA dramatically in mesenchy me from E13 to E15. BMP-3 mRNA expression were almost negative in either co ntrol or retinoic acid-treated groups during all stages. It was concluded t hat spatial and temporal expression of BMP-2,4,5 was required during normal palatogenesis, and that a deficiency of their mRNA expression may contribu te to the pathogenesis of cleft palate. (C) 2000 Elsevier Science Ltd. All rights reserved.