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Molecular mechanisms underlying cell-fate specification and cellular diversity of the trophoblast lineage during placental morphogenesis in mice

Placental morphogenesis is a highly dynamic process involving mutual recognition and interlacing between the trophoblast–uterus and ultimately the initiation of the maternal–fetal circulatory system. During placental morphogenesis in mice, the trophoblast lineage, which integrates maternal and fetal signaling, undergoes stage-specific changes in gene regulatory programs directing cellular proliferation and fate specification, generating diverse trophoblast subtypes. While accumulating evidence from studies on genetically engineered and mutant mice has revealed the involvement of cell-specific core transcription factors in certain key events during placental morphogenesis, the precise molecular mechanisms by which multipotent trophoblasts gradually differentiate into different subtypes are still largely unknown. In this review, we primarily focus on mutant mouse models with placental phenotypes to provide a comprehensive understanding of the molecular mechanisms underlying cell-fate specification and cellular diversity of the trophoblast lineage during the placental morphogenesis.