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Sequential formation and resolution of multiple rosettes drive embryo remodelling after implantation

Christodoulou, Neophytos and Kyprianou, Christos and Weberling, Antonia and Wang, Ran and Cui, Guizhong and Peng, Guangdun and Jing, Naihe and Zernicka-Goetz, Magdalena (2018) Sequential formation and resolution of multiple rosettes drive embryo remodelling after implantation. Nature Cell Biology, 20 (11). pp. 1278-1289. ISSN 1465-7392. https://resolver.caltech.edu/CaltechAUTHORS:20190408-111046061

[img] Image (JPEG) (Supplementary Figure 1: Analysis of extra-embryonic ectoderm tissue folding in embryos derived after decidua fixation) - Supplemental Material
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[img] Image (JPEG) (Supplementary Figure 2: ECM/ β1-integrin during extra-embryonic ectoderm and TSCs polarization) - Supplemental Material
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[img] Image (JPEG) (Supplementary Figure 3: Characterization of extra-embryonic ectoderm cells) - Supplemental Material
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[img] Image (JPEG) (Supplementary Figure 4: Epiblast remodelling upon hybrid rosette resolution) - Supplemental Material
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[img] Image (JPEG) (Supplementary Figure 5: Extra-embryonic ectoderm rosettes facilitate cavities extension and fusion) - Supplemental Material
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[img] Image (JPEG) (Supplementary Figure 6: Spatial transcriptome analysis of E5.25-E5.75 embryos) - Supplemental Material
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[img] Image (JPEG) (Supplementary Figure 7: Differential gene expression analysis of embryonic and extra-embryonic compartments) - Supplemental Material
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[img] Image (JPEG) (Supplementary Figure 8: Cell intercalation after initial cavities fusion results in the formation of a pseudostratified epithelium) - Supplemental Material
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[img] PDF (Supplementary Figures 1–8, Supplementary Table and Supplementary Movie legends) - Supplemental Material
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[img] MS Excel (Supplementary Table 1. Processed RNA-seq data) - Supplemental Material
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[img] MS Excel (Supplementary Table 2. Statistics source data) - Supplemental Material
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[img] Video (AVI) (Supplementary Video 1. Tissue-folding-mediated extra-embryonic cavity formation) - Supplemental Material
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[img] Video (AVI) (Supplementary Video 2. Tissue-folding-mediated extra-embryonic cavity formation in 3D) - Supplemental Material
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[img] Video (AVI) (Supplementary Video 3. Apical constriction during extra-embryonic ectoderm tissue folding) - Supplemental Material
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[img] Video (AVI) (Supplementary Video 4. 3D segmentation of representative extra-embryonic ectoderm rosettes) - Supplemental Material
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[img] Video (AVI) (Supplementary Video 5. 3D segmentation of neighbouring extra-embryonic ectoderm rosettes) - Supplemental Material
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[img] Video (AVI) (Supplementary Video 6. Hybrid rosette resolution precedes epiblast remodelling (1)) - Supplemental Material
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[img] Video (AVI) (Supplementary Video 7. Hybrid rosette resolution precedes epiblast remodelling (2)) - Supplemental Material
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[img] Video (AVI) (Supplementary Video 8. Laser ablation mediated hybrid rosette resolution) - Supplemental Material
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[img] Video (AVI) (Supplementary Video 9. Polarized tract connects the centre of a rosette with the embryonic cavity) - Supplemental Material
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[img] Video (AVI) (Supplementary Video 10. ExE rosettes facilitate epiblast cavity extension (1)) - Supplemental Material
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[img] Video (AVI) (Supplementary Video 11. ExE rosettes facilitate epiblast cavity extension (2)) - Supplemental Material
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[img] Video (AVI) (Supplementary Video 12. ExE rosettes facilitate extra-embryonic cavity extension) - Supplemental Material
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[img] Video (AVI) (Supplementary Video 13. Rosette-mediated embryonic and extra-embryonic cavities extension) - Supplemental Material
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[img] Video (AVI) (Supplementary Video 14. Extra-embryonic ectoderm cell intercalation upon initial cavities fusion) - Supplemental Material
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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.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1038/s41556-018-0211-3DOIArticle
https://rdcu.be/bvpNGPublisherFree ReadCube access -- Article
https://doi.org/10.1038/s41556-018-0245-6DOICorrection
https://rdcu.be/bvpPePublisherFree ReadCube access - Correction
ORCID:
AuthorORCID
Christodoulou, Neophytos0000-0003-4338-5847
Kyprianou, Christos0000-0001-8516-9195
Wang, Ran0000-0003-4956-5742
Peng, Guangdun0000-0002-8586-0637
Jing, Naihe0000-0003-1509-6378
Zernicka-Goetz, Magdalena0000-0002-7004-2471
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.
Funders:
Funding AgencyGrant Number
European Research Council (ERC)669198
Wellcome Trust098287/Z/12/Z
Marie Curie Fellowship721537
Biotechnology and Biological Sciences Research Council (BBSRC)UNSPECIFIED
Issue or Number:11
Record Number:CaltechAUTHORS:20190408-111046061
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20190408-111046061
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:94565
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:09 Apr 2019 15:00
Last Modified:09 Mar 2020 13:19

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