Regulated Expression of Homeobox GenesMsx-1andMsx-2in Mouse Mammary Gland Development Suggests a Role in Hormone Action and Epithelial–Stromal Interactions

AbstractThe murine homeobox genesMsx-1andMsx-2are related to theDrosophila mshgene and are expressed in a variety of tissues during mouse embryogenesis. We now report the developmentally regulated expression ofMsx-1andMsx-2in the mouse mammary gland and show that their expression patterns point toward significant functional roles.Msx-1andMsx-2transcripts were present in glands of virgin mice and in glands of mice in early pregnancy, but transcripts decreased dramatically during late pregnancy. Low levels ofMsx-1transcripts were detected in glands from lactating animals and during the first days of involution, whereasMsx-2expression was not detected during lactation or early involution. Expression of both genes increased gradually as involution progressed.Msx-2but notMsx-1expression was decreased following ovariectomy or following exposure to anti-estrogen implanted directly into the gland. Hormonal regulation ofMsx-2expression was confirmed when transcripts returned to normal levels after estrogen was administered to ovariectomized animals.In situmolecular hybridization forMsx-1showed transcripts localized to the mammary epithelium, whereasMsx-2expression was confined to the periductal stroma. Mammary stroma from which mammary epithelium had been removed did not transcribe detectable amounts ofMsx-2,showing that expression is regulated by contiguous mammary epithelium, and indicating a role for these homeobox genes in mesenchymal–epithelial interactions during mammary development