Morphogenesis of extra-embryonic tissues directs the remodelling of the mouse embryo at implantation
Abstract
Mammalian embryos change shape dramatically upon implantation. The cellular and molecular mechanism underlying this transition are largely unknown. Here, we show that this transition is directed by cross talk between the embryonic epiblast and the first extra-embryonic tissue, the trophectoderm. Specifically, we show via visualisation of a Cdx2-GFP reporter line and pharmacologically mediated loss and gain of function experiments that the epiblast provides FGF signal that results in differential fate acquisition in the multipotent trophectoderm leading to the formation of a tissue boundary within this tissue. The trophectoderm boundary becomes essential for expansion of the tissue into a multi-layered epithelium. Folding of this multi-layered trophectoderm induces spreading of the second extra-embryonic tissue, the primitive endoderm. Together, these events remodel the pre-implantation embryo into its post-implantation cylindrical shape. Our findings uncover how communication between embryonic and extra-embryonic tissues provides positional cues to drive shape changes in mammalian development during implantation.
Additional Information
© The Author(s) 2019. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. Received 08 February 2019. Accepted 03 July 2019. Published 07 August 2019. We are grateful to D. Glover, M. Shahbazi, M. Zhu, and C. Kyprianou for feedback on the manuscript. The M.Z.G lab is supported by grants from the European Research Council (669198) and the Welcome Trust (098287/Z/12/Z) and the EU Horizon 2020 Marie Sklodowska-Curie actions (ImageInLife,721537). Author Contrivutions: These authors contributed equally: Neophytos Christodoulou, Antonia Weberling. N.C. and A.W. designed and carried out the experiments and data analysis. D.S, K.I.A, and P.T. generated the E-cadherin-GFP transgenic line. N.C, A.W. and M.Z-G. wrote the manuscript. M.Z-G. conceived and supervised the project with the help of N.C. Data availability: The authors declare that all data supporting the findings of this study are available within the article and its supplementary information files or from the corresponding author upon reasonable request. The source data of Figs. 1d, 1h, 1i, 2c, 3a, 3d, 5c, 6a, and Supplementary Figs. S1b, S7a, S10c–d, S11a can be found as supplementary movies. The complete data supporting the results discussed in this study are available upon a reasonable request from the corresponding author. The source data underlying Figs. 2d, 3b, 3c, 3f, 4f, 5b, 6b–g, and Supplementary Figs. 3c, 5b, and 10c are provided as a Source Data file. The authors declare no competing interests. Peer review information: Nature Communications thanks Janet Rossant and other anonymous reviewer(s) for their contribution to the peer review of this work. Peer reviewer reports are available.Attached Files
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Additional details
- PMCID
- PMC6686005
- Eprint ID
- 102441
- Resolver ID
- CaltechAUTHORS:20200409-115738046
- European Research Council (ERC)
- 669198
- Wellcome Trust
- 098287/Z/12/Z
- Marie Curie Fellowship
- 721537
- Created
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2020-04-09Created from EPrint's datestamp field
- Updated
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2021-11-16Created from EPrint's last_modified field