MSX-2 EXPRESSION AND GLUCOCORTICOID-INDUCED OVEREXPRESSION IN EMBRYONIC MOUSE SUBMANDIBULAR GLANDS

It is well known that the process of branching morphogenesis requires epithelial-mesenchymal interactions. One outstanding model for the stu dy of tissue interactions during branching morphogenesis is the embryo nic mouse submandibular gland (SMG). Although it has been clearly demo nstrated that the branching pattern is dependent on interactions betwe en the epithelium and the surrounding mesenchyme, little is known abou t the molecular mechanism underlying the branching process. One group of transcription factors that likely participates in the control of ep ithelial-mesenchymal inductive interactions are the Msx-class of homeo domain-containing proteins. In this paper, we focus on Msx-2 because i ts developmental expression is correlated with inductive interactions, suggesting that Msx-2 may play a functional role during cell-cell int eractions. We demonstrate the expression of Msx-2 mRNA and protein to be primarily in the branching epithelia with progressive embryonic (E1 3 to E15) SMG development and, to a lesser extent, in the mesenchyme. We also show that Msx-2 is expressed by embryonic SMG primordia cultur ed under defined conditions. In addition, to begin to delineate a func tional role for Msx-2, we employed an experimental strategy by using e xogenous glucocorticoid (CORT) treatment of embryonic SMGs in vitro an d in vivo to significantly enhance branching morphogenesis and evaluat e the effect of CORT treatment on embryonic SMG Msx-2 expression. A ma rked increase in Msx-2 transcripts and protein is detected with in vit ro and in vivo CORT treatment. Our studies indicate that one mechanism of CORT regulation of salivary gland morphogenesis is likely through the modulation of Msx-2 gene expression.