The amnion is a transient extra-embryonic tissue whose formation, known as amniogenesis, is vital to amniote embryogenesis. The growing body of knowledge on amniotic lineage emergence and functions has enabled a more comprehensive understanding of the underlying molecular mechanisms and thus may inspire future improvement in stem cell-based amniogenic models. In this Review we first introduce cavitation amniogenesis as a hallmark of human peri-implantation embryogenesis before addressing how cavitation amniogenesis is similar in humans and non-human primates but contrasts with folding amniogenesis in other amniotes such as mice and pigs. We also highlight the ongoing debate of whether primate amniogenesis harbours lineage plasticity for specifying germ cell fate and further discuss the two-wave amniogenesis model and its basis on the pluripotency transition. Finally, we summarize the potential of the recent stem cell-based human embryo models in elucidating amniotic formation and functions.
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