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

M Simunovic, JJ Metzger, F Etoc, A Yoney, A Ruzo… - Nature cell …, 2019 - nature.com
M Simunovic, JJ Metzger, F Etoc, A Yoney, A Ruzo, I Martyn, G Croft, DS You, AH Brivanlou…
Nature cell biology, 2019nature.com
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 …
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.
nature.com
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