Developmental expression and CORT-regulation of TGF-β and EGF receptor mRNA during mouse palatal morphogenesis: Correlation between CORT-induced cleft palate and TGF-β2 mRNA expression

摘要: Glucocorticoids (CORT) have been shown to induce cleft palate in mice. Although the pathogenetic pathway of CORT-induced has investigated for several decades, molecular details remain be elucidated. Since growth factors regulate morphogenesis, and expression or their receptors, e.g. TGF-beta, EGF receptor (EGF-R), are known modulated by CORT, we postulate that CORT modulation factor (or receptor) gene is a key mechanism involved palate. To test this hypothesis, analyzed steady-state levels (Northern RNase protection) developmental (in situ hybridization) four CORT-responsive genes--TGF-Beta 1, TGF- beta 2, TGF-beta 3, (EGF-R)--in developing mouse palates presence absence exogenous CORT. Pregnant B10.A dams were injected on day 12 gestation with sham-injected embryonic collected at 3 days postinjection (E13-E15). During development, significant increases 1 mRNA levels, as well decrease 2 detected; no difference EGF-R transcript level observed progressive development. In CORT-exposed palates, demonstrate differences direction magnitude change time compared controls. However, delays down-regulation palatal normally seen 14 gestation. inhibit cell proliferation. The mRNA, only isoform primarily expressed mesenchyme, significantly decreases development; associated increased mesenchymal proliferation shelf growth. critical stage palatogenesis, induces delay normal expression. Given growth, conclude probably event pathogenesis