MASH2 ACTS CELL AUTONOMOUSLY IN MOUSE SPONGIOTROPHOBLAST DEVELOPMENT

The Mash2 gene, which encodes a basic helix-loop-helix transcription f actor, is one of the mammalian homologues of the Drosophila achaete-sc ute genes. It is strongly expressed in diploid trophoblast cells of th e postimplantation mouse embryo. Targeted mutagenesis of Mash2 reveale d that loss of function results in embryonic lethality at midgestation , due to placental failure associated with a lack of spongiotrophoblas t and reduced labyrinthine trophoblast layers. For the further study o f Mash2 function in development of the trophoblast cell lineage, we ha ve performed chimeric analysis combining Mash2 mutant and wild-type em bryos. We have addressed the question of whether the phenotype of the Mash2 mutant embryo, which affects all of the three trophoblast cell l ayers, is caused by a cell autonomous or non-autonomous defect and whe ther Mash2 is required in both spongiotrophoblast and labyrinthine tro phoblast development. Our results showed no contribution of Mash2 muta nt cells to the spongiotrophoblast layer in chimeric placentae at 10.5 and 12.5 days postcoitum, suggesting that the product of the Mash2 ge ne is required cell autonomously during the development of the spongio trophoblast. However, it seems that Mash2 is not required for developm ent of labyrinthine trophoblast or giant cells, since high contributio ns of Mash2 mutant cells were observed in those trophoblast cell layer s in the chimeric placentae analyzed. We can therefore conclude that t he primary and cell-autonomous function of Mash2 appears to be an invo lvement in the development of diploid trophoblast cells in the ectopla cental cone to form the spongiotrophoblast cell layer of the mature ch orioallantoic placenta. (C) 1997 Academic Press.