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

Cornell Affiliated Author(s)


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


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. © 2019, The Author(s), under exclusive licence to Springer Nature Limited.

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Nature Cell Biology





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