Mechanical perspectives on the anterior-posterior axis polarization of mouse implanted embryos

In most mammals, embryonic development and growth proceed in the maternal uterus. Mouse late blastocyst embryos implant on the uterine epithelium around embryonic day (E)4.5, and immediately afterward the whole embryo's shape is dynamically changed from a bowl-like shape to an elongated egg-cylinder until E5.5. Concurrently, mouse anterior-posterior (A-P) axis polarization occurs by the emergence of distal visceral endoderm (DVE) cells at the cellular and molecular levels as the proximal-distal (P-D) axis. The embryonic growth and axis polarization are considered to be controlled primarily by multiple growth factors' signaling. However, the precise cellular mechanisms of DVE formation in which this signaling is involved have been unclear. We recently identified that local breaching of the basement membrane (BM) between the epiblast and the visceral endoderm (VE) at the distal tip allows inner epiblast cells to transmigrate into the outer VE layer as the emergence of DVE cells. More importantly, the local BM loss in the distal region appears to be triggered by mechanical forces exerted from maternal tissues on embryos and embryonic growth itself. Our data suggest a fascinating hypothesis concerning mouse A-P axis polarization mediated by the whole embryo's shape change through mechanical stress between the embryo and the uterine epithelium. Our mechanical model provides a unique insight into why the first axis polarity of the implanted mouse embryo is established in the P-D direction initially and not in the future A-P direction. We also discuss whether the local breaching of the BM mediated by mechanical cues is essential to mouse A-P axis polarization in in vitro culture.