Glucocorticoid receptor expression during the development of the embryonic mouse secondary palate

The role of glucocorticoids and their interaction with the glucocorticoid receptor (GR) during embryonic growth and development has been a topic of interest and research for many years. Glucocorticoids are known to be teratogenic, and administration of these compounds during pregnancy produces cleft palate in the offspring. In the mouse, induction of cleft palate correlates with the level of palatal glucocorticoid receptor (GR) expression. However, the specific patterns of GR expression during critical stages of palatal morphogenesis remain to be examined. In the present study, GR expression was evaluated in the developing palates of C57BL/6N mouse embryos on gestation days (GD) 12, 13, 14, and 15 by both in situ hybridization and immunohistochemistry. On GD 12, GR mRNA was locally expressed in the region of palatal shelf outgrowth in both mesenchymal and epithelial cells, and GR was expressed uniformly throughout the developing shelf. A similar pattern of distribution occurred on GD 13 as the shelf became larger and elevated. By GD 14, GR was regionally expressed with higher levels in epithelial cells relative to mesenchyme. Chondrogenic regions strongly expressed GR. In different regions of oral and nasal epithelia localized patterns of expression were noted and may be related to differentiated state. Correspondingly, GR mRNA was expressed in epithelia and became regional in mesenchyme with abundant mRNA in regions of bone formation. On GD 15, oral and nasal epithelial cells showed mRNA, but mesenchymal levels were low except for chondrogenic regions. This pattern correlated with immunohistochemical localization of GR on GD 15. During palatogenesis the expression of mRNA correlated with immunodetectable GR peptide. GR localized initially within regions of active morphogenesis and subsequently within differentiating cells. This specificity of spatial and temporal expression supports the idea that GR is involved in regulation of regional growth and differentiation during palatogenesis.