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| Item Type: | Article |
|---|---|
| Title: | A 3D model of a human epiblast reveals BMP4-driven symmetry breaking |
| Creators Name: | Simunovic, M., Metzger, J.J., Etoc, F., Yoney, A., Ruzo, A., Martyn, I., Croft, G., You, D.S., 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 |
| ISSN: | 1465-7392 |
| Publisher: | Nature Publishing Group |
| Volume: | 21 |
| Number: | 7 |
| 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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