Prediction and control of symmetry breaking in embryoid bodies by environment and signal integration

Naor Sagy, Shaked Slovin, Maya Allalouf, Maayan Pour, Gaya Savyon, Jonathan Boxman, Iftach Nachman*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

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 mouse embryoid bodies (EBs), we studied how contact, biochemical cues and neighboring cell cues affect the positioning of a primitive streak-like locus and thus determine the anteroposterior 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, probably through modulation of chemical cues rather than by mechanical signaling. We can push or pull Bra onset away from contact points by introducing a separate localized Wnt signal source, or maneuver Bra onset to a few loci or to an isotropic peripheral pattern. Furthermore, we show that Foxa2-positive 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 could prove valuable for in vitro differentiation and organoid formation.

Original languageEnglish
Article numberdev181917
JournalDevelopment (Cambridge)
Volume146
Issue number20
DOIs
StatePublished - 2019

Keywords

  • Brachyury
  • Embroid bodies
  • Gastruloids
  • Mouse
  • Organoids
  • Symmetry breaking

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