Sequential formation and resolution of multiple rosettes drive embryo remodelling after implantation
Abstract
The morphogenetic remodelling of embryo architecture after implantation culminates in pro-amniotic cavity formation. Despite its key importance, how this transformation occurs remains unknown. Here, we apply high-resolution imaging of embryos developing in vivo and in vitro, spatial RNA sequencing and 3D trophoblast stem cell models to determine the sequence and mechanisms of these remodelling events. We show that cavitation of the embryonic tissue is followed by folding of extra-embryonic tissue to mediate the formation of a second extra-embryonic cavity. Concomitantly, at the boundary between embryonic and extra-embryonic tissues, a hybrid 3D rosette forms. Resolution of this rosette enables the embryonic cavity to invade the extra-embryonic tissue. Subsequently, β1-integrin signalling mediates the formation of multiple extra-embryonic 3D rosettes. Podocalyxin exocytosis leads to their polarized resolution, permitting the extension of embryonic and extra-embryonic cavities and their fusion into a unified pro-amniotic cavity. These morphogenetic transformations of embryogenesis reveal a previously unappreciated mechanism for lumen expansion and fusion.
Additional Information
© 2018 Springer Nature Publishing AG. Received: 8 February 2018; Accepted: 6 September 2018; Published online: 15 October 2018. We are grateful to D. Glover, F. Antonica, M. Shahbazi, G. Amadei and S. Harrison for feedback on the manuscript. We also thanks J. Nichols for the Confetti TSCs, I. Roswell (Francis Crick Institute) for LifeAct-GFP mice and K. O'Holleran (Cambridge Advanced Imaging Center) for help with the laser ablation experiments. 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). C.K. is supported by the BBSRC Doctoral training studentship. These authors contributed equally: Neophytos Christodoulou, Christos Kyprianou. Author Contributions: N.C. and C.K. designed and carried out the experiments and data analysis. A.W. contributed to embryo live imaging. G.C. and G.P. performed the embryo cryosection, laser microdissection and library construction experiments for RNA-seq. R.W. carried out the RNA-seq analysis. N.J. supervised the work related to spatial trancriptome analysis. M.Z.-G. conceived and supervised the study and wrote the manuscript with the help of N.C. and C.K. Data availability: RNA-seq data that support the findings of this study have been deposited in the Gene Expression Omnibus (GEO) under accession code GSE110808. Source data for Figs. 1b, 2c,e,g,i,j,l and 3c,h and Supplementary Fig. 3c,d have been provided as Supplementary Table 2. Source data for Fig. 1g,h, 3e,f, 4d,f and 5c,d and Supplementary Fig. 3c are provided as Supplementary Videos. All other data supporting the findings of this study are available from the corresponding author on reasonable request. The authors declare no competing interests. Change history: 19 November 2018 -- In the version of this Article originally published, the first name of author Guangdun Peng was spelled incorrectly as Guangdum. This has now been amended in all versions of the Article.Errata
Correction to: Nature Cell Biology https://doi.org/10.1038/s41556-018-0211-3, published online 15 October 2018. In the version of this Article originally published, the first name of author Guangdun Peng was spelled incorrectly as Guangdum. This has now been amended in all versions of the Article.Attached Files
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Additional details
- Eprint ID
- 94565
- Resolver ID
- CaltechAUTHORS:20190408-111046061
- 669198
- European Research Council (ERC)
- 098287/Z/12/Z
- Wellcome Trust
- 721537
- Marie Curie Fellowship
- Biotechnology and Biological Sciences Research Council (BBSRC)
- Created
-
2019-04-09Created from EPrint's datestamp field
- Updated
-
2023-06-01Created from EPrint's last_modified field