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A 3D model of a human epiblast reveals BMP4-driven symmetry breaking
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A 3D model of a human epiblast reveals BMP4-driven symmetry breaking
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A 3D model of a human epiblast reveals BMP4-driven symmetry breaking
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Journal Article
A 3D model of a human epiblast reveals BMP4-driven symmetry breaking
2019
Overview
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.
Simunovic et al. use human embryonic stem cells to generate a three-dimensional model of a human pre-gastrulation epiblast and show that anterior–posterior symmetry breaking can be induced by BMP4 and WNT signalling.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 631/136
/ 96/106
/ 96/63
/ Biomedical and Life Sciences
/ Bone Morphogenetic Protein 4 - metabolism
/ Cellular signal transduction
/ Embryos
/ Epithelial-Mesenchymal Transition
/ Gene Expression Regulation, Developmental - physiology
/ Humans
/ Polarity
/ Primitive Streak - embryology
/ Primitive Streak - metabolism
/ Signal Transduction - physiology
/ Symmetry
