Citation: Berenika Plusa, Anna Piliszek, Stephen Frankenberg, Jérôme Artus, Anna-Katerina Hadjantonakis,
(2008)
Distinct sequential cell behaviours direct primitive endoderm formation in the mouse blastocyst. Development (Cambridge, England) 135(18): Full text doi:10.1242/dev.021519

Mouse blastocyst at day 4 of development. Epiblast-specific marker Nanog (red) and primitive endoderm-specific expression of GFP from the Pdgfra promoter (green) are mutually exclusive and sorted into two adjacent layers.
This study examines the mechanisms by which two of the very earliest cell types become allocated in the mammalian embryo. During the earliest stages of development after fertilisation, the mammalian embryo begins to differentiate into three distinct cell types: the epiblast, which ultimately gives rise to all the tissues of the adult, and the trophectoderm and the primitive endoderm, which both contribute to tissues of the placenta. The first cell type to emerge is the trophectoderm, which is specified by the positions of cells located on the outside of the embryo. The trophectoderm thus surrounds the remaining inside cells, termed the inner cell mass (ICM), and a fluid filled cavity, to comprise the blastocyst stage of development. The ICM then segregates into epiblast and primitive endoderm cell types.
How this latter process occurs is only recently beginning to be understood. Previously it was believed that ICM cells lining the cavity become specified to form primitive endoderm by their position, while remaining ICM cells become epiblast by default. By contrast, more recent evidence suggests that already-specified primitive endoderm precursor cells are scattered, apparently randomly, throughout the inner cell mass and then migrate to their final position lining the cavity. In our study, we have used transgenic mouse embryos expressing a green fluorescent protein (GFP) in primitive endoderm cells. By tracing the movements of GFP-expressing cells from earlier stages of development by live time-lapse fluorescence imaging and examining the dynamic expression of various epiblast- and primitive endoderm-specific markers, we have shown that primitive endoderm formation is rather a more complex process than either the old model or the newer model suggest.
Thus, while movements of primitive endoderm precursor cells do occur within the ICM, positional information nevertheless appears to play some role in their definitive specification to primitive endoderm. Exactly how these various mechanisms balance out to achieve an optimal allocation of each cell type is the subject of our current research.
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