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

Cornell Affiliated Author(s)

Author

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

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

Date Published

Journal

Nature Cell Biology

Volume

21

Issue

7

Number of Pages

900-910,

URL

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85068224362&doi=10.1038%2fs41556-019-0349-7&partnerID=40&md5=b97c8920a226725be22d77939b74d8c5

DOI

10.1038/s41556-019-0349-7

Research Area

Funding Source

1502151
R01 GM101653
R01HD080699

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