OCT-4 TRANSCRIPTION FACTOR IS DIFFERENTIALLY EXPRESSED IN THE MOUSE EMBRYO DURING ESTABLISHMENT OF THE FIRST 2 EXTRAEMBRYONIC CELL LINEAGESINVOLVED IN IMPLANTATION

Oct-4 is the earliest expressed gene known to encode a transcription f actor which is developmentally regulated during mammalian embryogenesi s. In order to understand the role of Oct-4 in early murine embryogene sis, we carried out an analysis of the temporal and spatial pattern of protein expression. We report the presence of Oct-4 protein in cultur ed cells and murine embryos as determined by immunohistochemistry usin g confocal microscopy. Oct-4 protein is present in both embryonic stem cells and embryonal carcinoma cells, but is down-regulated following differentiation of these cells by culture in the absence of leukemia i nhibitory factor or in the presence of retinoic acid, respectively. In embryos, the protein is found at low levels in unfertilized eggs and is localized predominantly to the pronuclei upon their formation follo wing fertilization. The protein is present in the nuclei in all cleava ge stages, but following differentiation of the trophectoderm at the b lastocyst stage, Oct-4 protein is only expressed in the inner cell mas s. The pattern of protein expression to this stage correlates well wit h previously reported in situ hybridization results; however, a striki ng difference was seen in primitive endoderm cells which had begun to differentiate and migrate along the inner surface of the trophectoderm . In direct contrast to RNA localization studies which demonstrate tha t there are only low levels of Oct-4 transcripts in primitive endoderm cells, protein expression in these early migrating cells is higher th an in the inner cell, mass. (C) 1994 Academic Press, Inc.