Self-organized pendulum of inductions between the epiblast and extraembryonic endoderm support post-implantation progression of mouse blastoids

Embryos form partly by tissue self-organization caused by nonlinear cell interactions. Here, we create a partial mouse embryo model to decipher self-organizing principles underlying the co-development of the epiblast (Epi) and Extraembryonic endoderm (XEn). We activate naive embryonic stem cells to form a late blastocyst Epi/XEn-like niche (3D, hydrogel-free, serum-free). Once established, these two lineages autonomously progress in minimal medium to form an inner pro-amniotic-like cavity surrounded by a polarized Epi, and covered with visceral endoderm (VE)-like cells. We observe that progression occurs through a sequence of reciprocal inductions by which the Epi supports the primitive endoderm (PrE) to produce a basal lamina that subsequently regulates Epi polarization/cavitation, which, in return, channels the transcriptomic progression to Visceral endoderm (VE). Finally, the VE contributes to Epi bifurcation into both anterior- and posterior-like states. Similarly, boosting the formation of PrE-like cells within blastoids supports developmental progression. Overall, we argue that self-organization can arise from a pendulum of lineages inductions propagating overtime.