A pendulum of induction between the epiblast and extra-embryonic endoderm supports post-implantation progression.

  • publication
  • 23-08-2022

Vrij EJ, Scholte Op Reimer YS, Roa Fuentes L, Misteli Guerreiro I, Holzmann V, Frias Aldeguer J, Sestini G, Koo BK, Kind J, van Blitterswijk CA, Rivron NC. Development 2022 Oct;149(20):. PMC9534490. 10.1242/dev.192310. 276399.

Embryogenesis is supported by dynamic loops of cellular interactions. Here, we create a partial mouse embryo model to elucidate the principles of epiblast (Epi) and extra-embryonic endoderm co-development (XEn). We trigger naive mouse embryonic stem cells to form a blastocyst-stage niche of Epi-like cells and XEn-like cells (3D, hydrogel free and serum free). Once established, these two lineages autonomously progress in minimal medium to form an inner pro-amniotic-like cavity surrounded by polarized Epi-like cells covered with visceral endoderm (VE)-like cells. The progression occurs through reciprocal inductions by which the Epi supports the primitive endoderm (PrE) to produce a basal lamina that subsequently regulates Epi polarization and/or cavitation, which, in return, channels the transcriptomic progression to VE. This VE then contributes to Epi bifurcation into anterior- and posterior-like states. Similarly, boosting the formation of PrE-like cells within blastoids supports developmental progression. We argue that self-organization can arise from lineage bifurcation followed by a pendulum of induction that propagates over time.

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