DEVELOPMENTAL RESTRICTION OF MASH-2 EXPRESSION IN TROPHOBLAST CORRELATES WITH POTENTIAL ACTIVATION OF THE NOTCH-2 PATHWAY

Mash-2 expression begins during preimplantation development, but is re stricted to trophoblasts after the blastocyst stage. Within the iropho biasi lineage, Mash-2 transcripts are first expressed in the ectoplace ntal cone and chorion, but not in terminally differentiated trophoblas t giant ce Is. After day 8.5 of gestation, Mash-2 expression becomes f urther restricted io focal sites within the spongiotrophoblast and lab yrinth. Downregulation is probably important for normal development si nce overexpression of Mash-2 reduces giant cell formation. We have inv estigated the role that the Notch signaling pathway may play in tropho blast development. Mash-2 is a homologue of Drosophila achaete/scute c omplex genes. in Drosophila, activation of the Notch receptor induces transcriptional repressors encoded by the hairy/Enhancer of split (HES ) genes, which interact with the Groucho protein to shut off achaete-s cute transcription. In the developing mouse placenta, we found that al l elements of the Notch pathway were expressed. In particular, the Noi ch-2, HES-2, and HES-3 genes were coexpressed in trophoblast giant cel ls and in foci within the spongiotrophoblast at day 10.5 when Mash-2 t ranscription becomes restricted. Two members of the mammalian Groucho family were expressed in trophoblasts; TLE3 was expressed broadly in t he giant cell, spongiotrophoblast, and labyrinthine regions, whereas T LE2 was limited io giant cells and focal regions of the spongiotrophob last. These data suggest that Notch signaling through activation of HE S transcriptional repressors may play a role in murine placental devel opment. (C) 1997 Wiley-Liss, Inc.