Trophoblast lineage specification in the mammalian preimplantation embryo

BACKGROUND: The establishment of the trophectoderm (TE) and the inner cell mass (ICM) is the first cell lineage segregation that occurs in mammalian preimplantation development. TE will contribute to the placenta while ICM cells give rise to the epiblast (EPI) and primitive endoderm (PrE). There are two historical models for TE/ICM segregation: the positional (inside‐outside) model and the polarity model, but both models alone cannot explain the mechanism of TE/ICM segregation. METHODS: This article discusses a current possible model based on recent studies including the finding through live‐cell imaging of the expression patterns of caudal type homeobox 2 (Cdx2), a key transcription factor of TE differentiation in the mouse embryo. RESULTS: It was observed that a part of outer Cdx2‐expressing blastomeres was internalized at the around 20‐ to 30‐cell stage, downregulates Cdx2, ceases TE differentiation, and participates in ICM lineages. CONCLUSION: The early blastomere, which starts differentiation toward the TE cell fate, still has plasticity and can change its fate. Differentiation potency of all blastomeres until approximately the 32‐cell stage is presumably not irreversibly restricted even if they show heterogeneity in their epigenetic modifications or gene expression patterns.