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

Item Type:Article
Title:A 3D model of a human epiblast reveals BMP4-driven symmetry breaking
Creators Name:Simunovic, M. and Metzger, J.J. and Etoc, F. and Yoney, A. and Ruzo, A. and Martyn, I. and Croft, G. and You, D.S. and Brivanlou, A.H. and Siggia, E.D.
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.
Keywords:Bone Morphogenetic Protein 4, Cell Polarity, Epithelial-Mesenchymal Transition, Gastrulation, Developmental Gene Expression Regulation, Germ Layers, Primitive Streak, Signal Transduction, Tissue Culture Techniques
Source:Nature Cell Biology
Publisher:Nature Publishing Group
Page Range:900-910
Date:July 2019
Official Publication:https://doi.org/10.1038/s41556-019-0349-7
PubMed:View item in PubMed

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