Dynamic expression of Lrp2 pathway members reveals progressive epithelial differentiation of primitive endoderm in mouse blastocyst

Mesenchyme to epithelium transitions are crucial to embryonic development. The early mouse embryo offers an excellent model to study epithelium formation as during the first three days of development two epithelia are formed, the trophectoderm (TE) and the primitive endoderm (PrE). We have previously shown that PrE cells are determined within the blastocyst ICM long before epithelium formation. In this work, we isolated Lrp2 as a novel PrE precursor (pre-PrE) marker by using a microarray strategy that combines a transcriptome analysis of three stem cell lines and early embryos. A detailed expression analysis shows that Lrp2 expression is induced in late E3.5 embryos indicating that pre-PrE cells are progressively maturing prior to polarization into an epithelium. Furthermore, the subcellular location of Lrp2, Disabled-2 (Dab2) and Collagen-IV shows that the epithelial structure is acquired in individual cells through successive steps.