Mouse anterior-posterior axis polarization is preceded by formation of the distal visceral endoderm (DVE) by unknown mechanisms. Here, we show by in vitro culturing of embryos immediately after implantation in microfabricated cavities that the external mechanical cues exerted on the embryo are crucial for DVE formation, as well as the elongated egg cylinder shape, without affecting embryo-intrinsic transcriptional programs except those involving DVE-specific genes. This implies that these developmental events immediately after implantation are not simply embryo-autonomous processes but require extrinsic factors from maternal tissues. Moreover, the mechanical forces induce a breach of the basement membrane barrier at the distal portion locally, and thereby the transmigrated epiblast cells emerge as the DVE cells. Thus, we propose that external mechanical forces exerted by the interaction between embryo and maternal uterine tissues directly control the location of DVE formation at the distal tip and consequently establish the mammalian primary body axis.
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