During early embryogenesis, mechanical constraints and localized biochemical signals co-occur around anteroposterior axis determination and symmetry breaking. Their relative roles, however, are hard to tease apart in vivo. Using Brachyury (Bra), a primitive streak and mesendoderm marker in EBs, we study how contact, biochemical and neighboring cell cues affect the positioning of a primitive streak-like locus, determining the AP axis. We show that a Bra-competent layer must be formed in the EB before Bra expression initiates, and that Bra onset locus position is biased by contact points of the EB with its surrounding, likely through chemical cues modulation rather than by mechanical signaling. We can push or pull Bra onset away from contact points by introducing a separate localized Wnt signal source, maneuver Bra onset to a few loci, or to an isotropic peripheral pattern. Finally, we show Foxa2+ cells are predictive of the future location of Bra onset, demonstrating an earlier symmetry-breaking event. Our analysis of factors affecting symmetry breaking and spatial fate choice during this developmental process may prove valuable for in vitro differentiation and organoid formation.
Prediction and control of symmetry breaking in embryoid bodies by environment and signal integration
Currently Viewing Accepted Manuscript - Newer Version Available
Naor Sagy, Shaked Slovin, Maya Allalouf, Maayan Pour, Gaya Savyon, Jonathan Boxman, Iftach Nachman; Prediction and control of symmetry breaking in embryoid bodies by environment and signal integration. Development 2019; dev.181917. doi: https://doi.org/10.1242/dev.181917
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