Recording morphogen signals reveals mechanisms underlying gastruloid symmetry breaking

Nat Cell Biol. 2024 Nov;26(11):1832-1844. doi: 10.1038/s41556-024-01521-9. Epub 2024 Oct 2.

Abstract

Aggregates of stem cells can break symmetry and self-organize into embryo-like structures with complex morphologies and gene expression patterns. Mechanisms including reaction-diffusion Turing patterns and cell sorting have been proposed to explain symmetry breaking but distinguishing between these candidate mechanisms of self-organization requires identifying which early asymmetries evolve into subsequent tissue patterns and cell fates. Here we use synthetic 'signal-recording' gene circuits to trace the evolution of signalling patterns in gastruloids, three-dimensional stem cell aggregates that form an anterior-posterior axis and structures resembling the mammalian primitive streak and tailbud. We find that cell sorting rearranges patchy domains of Wnt activity into a single pole that defines the gastruloid anterior-posterior axis. We also trace the emergence of Wnt domains to earlier heterogeneity in Nodal activity even before Wnt activity is detectable. Our study defines a mechanism through which aggregates of stem cells can form a patterning axis even in the absence of external spatial cues.

MeSH terms

  • Animals
  • Body Patterning* / genetics
  • Cell Aggregation
  • Gastrula / metabolism
  • Gene Expression Regulation, Developmental*
  • Gene Regulatory Networks
  • Nodal Protein / genetics
  • Nodal Protein / metabolism
  • Organoids / metabolism
  • Signal Transduction
  • Stem Cells / metabolism
  • Wnt Proteins / genetics
  • Wnt Proteins / metabolism
  • Wnt Signaling Pathway

Substances

  • Wnt Proteins
  • Nodal Protein