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Nat Cell Biol. 2019 Jul;21(7):900-910. doi: 10.1038/s41556-019-0349-7. Epub 2019 Jul 1.

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

Author information

1
Laboratory of Stem Cell Biology and Molecular Embryology, The Rockefeller University, New York, NY, USA.
2
Center for Studies in Physics and Biology, The Rockefeller University, New York, NY, USA.
3
Laboratory of Stem Cell Biology and Molecular Embryology, The Rockefeller University, New York, NY, USA. brvnlou@rockefeller.edu.
4
Center for Studies in Physics and Biology, The Rockefeller University, New York, NY, USA. siggiae@rockefeller.edu.

Abstract

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.

PMID:
31263269
DOI:
10.1038/s41556-019-0349-7

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