An advanced head-to-tail mouse embryo model with hypoxia-mediated neural patterning

The dynamic cell-cell and cell-environment interactions that together shape the embryo largely remained unexplorable until the advance of stem cell-based embryo models. These revealed the self-organizing properties of cells in response to endogenous and exogenous cues.

Among the latter, restricted oxygen (hypoxia) emerged as a critical microenvironmental regulator that influences cell type diversification in multicellular systems. Here we built a modular ESC-based head-to-tail model of mouse embryogenesis by developing an antero-posterior (AP) assembly strategy under hypoxia. These structures - called HAP-gastruloids - feature stage-appropriate anterior neural tissues that recapitulate the morphological organization and transcriptional identity of fore- and midbrain including spatial organizer regions such as the midbrain-hindbrain boundary.