A 3D model of a human epiblast reveals BMP4-driven symmetry breaking


  • M. Simunovic
  • J.J. Metzger
  • F. Etoc
  • A. Yoney
  • A. Ruzo
  • I. Martyn
  • G. Croft
  • D.S. You
  • A.H. Brivanlou
  • E.D. Siggia


  • Nature Cell Biology


  • Nat Cell Biol 21 (7): 900-910


  • Breaking the anterior-posterior symmetry in mammals occurs at gastrulation. Much of the signalling network underlying this process has been elucidated in the mouse; however, there is no direct molecular evidence of events driving axis formation in humans. Here, we use human embryonic stem cells to generate an in vitro three-dimensional model of a human epiblast whose size, cell polarity and gene expression are similar to a day 10 human epiblast. A defined dose of BMP4 spontaneously breaks axial symmetry, and induces markers of the primitive streak and epithelial-to-mesenchymal transition. We show that WNT signalling and its inhibitor DKK1 play key roles in this process downstream of BMP4. Our work demonstrates that a model human epiblast can break axial symmetry despite the absence of asymmetry in the initial signal and of extra-embryonic tissues or maternal cues. Our three-dimensional model is an assay for the molecular events underlying human axial symmetry breaking.