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Developmental clock and mechanism of de novo polarization of the mouse embryo

Zhu, Meng and Cornwall-Scoones, Jake and Wang, Peizhe and Handford, Charlotte E. and Na, Jie and Thomson, Matt and Zernicka-Goetz, Magdalena (2020) Developmental clock and mechanism of de novo polarization of the mouse embryo. Science, 370 (6522). Art. No. eabd2703. ISSN 0036-8075. https://resolver.caltech.edu/CaltechAUTHORS:20201210-161600958

[img] PDF (Materials and Methods; Supplementary Text; Figs. S1 and S12; Tables S1 to S4; Captions for Movies S1 to S15; References) - Supplemental Material
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[img] PDF (MDAR Reproducibility Checklist) - Supplemental Material
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[img] Video (QuickTime) (Movie S1. Time-lapse imaging of control sister cell and resected sister cell expressing Ezrin-RFP developing from 4-cell stage to blastocyst stage from experiment illustrated in Figure 1e. Scale bars, 15μm) - Supplemental Material
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[img] Video (QuickTime) (Movie S2. Time-lapse imaging of control sister pair or resected sister pair expressing Ezrin-RFP developing from 4-cell stage to blastocyst stage from experiment illustrated in Supplementary Fig. 4a) - Supplemental Material
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[img] Video (QuickTime) (Movie S3. Time-lapse imaging of the natural apical domains formation process in a control embryo expressing Ezrin-RFP during the 4- to 8-cell stage development) - Supplemental Material
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[img] Video (QuickTime) (Movie S4. Time-lapse imaging of the membrane protrusions formation induced by Tead4 and Tfpa2c overexpression at the late 4-cell stage) - Supplemental Material
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[img] Video (QuickTime) (Movie S5. Time-lapse imaging of the membrane disorganization induced by RhoAQ63L overexpression at the late 4-cell stage) - Supplemental Material
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[img] Video (QuickTime) (Movie S6. Time-lapse imaging of the apical domains formation induced by Tead4, Tfap2c and RhoA-Q63L overexpression) - Supplemental Material
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[img] Video (QuickTime) (Movie S7. Natural embryo injected with Ezrin-RFP mRNA in whole embryo, and LifeAct-GFP mRNA in half of the embryo at the 2-cell stage, developing from 4- to late morula stage) - Supplemental Material
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[img] Video (QuickTime) (Movie S8. Embryo injected with Ezrin-RFP mRNA in whole embryo, and Tead4, Tfap2c, RhoA-Q63L and LifeAct-GFP mRNA in half of the embryo, developing from 4- to late morula stage) - Supplemental Material
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[img] Video (QuickTime) (Movie S9. Gata3-GFP transgenic embryo injected with Ezrin-RFP mRNA in half of the embryos developing from 8- to the blastocyst stage. Gata3-GFP signal appears from the 16-cell stage in the control embryo) - Supplemental Material
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[img] Video (QuickTime) (Movie S10. Gata3-GFP transgenic embryo injected with Ezrin-RFP and Tead4, Tfap2c and RhoA-Q63L mRNA in half of the embryos developing from 8- to the blastocyst stage. Gata3-GFP signal is upregulated at the late 8-cell stage in the overexpressed cells...) - Supplemental Material
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[img] Video (QuickTime) (Movie S11. Natural embryo injected with Ezrin-RFP (whole embryo) and LifeAct-GFP (half of the embryo) mRNA imaged from mid 8-cell stage to the late 8-cell stage) - Supplemental Material
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[img] Video (QuickTime) (Movie S12. Natural embryo injected with Ezrin-RFP and LifeAct-GFP mRNA imaged from mid 8-cell to late 8-cell stage with short time-interval to reveal Ezrin and Actin dynamics) - Supplemental Material
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[img] Video (QuickTime) (Movie S13. Natural embryo injected with Ezrin-RFP and LifeAct-GFP mRNA imaged at the mid 8-cell stage prior to the development of the apical domain) - Supplemental Material
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[img] Video (QuickTime) (Movie S14. PIV analysis of the natural embryo injected with LifeAct-GFP mRNA imaged at the mid 8-cell stage prior to the development of the apical domain) - Supplemental Material
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[img] Video (QuickTime) (Movie S15. Embryos injected with Ezrin-RFP and LifeAct-GFP mRNA were treated with Blebbstatin and imaged at the mid 8-cell stage prior to the development of the apical domain) - Supplemental Material
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Abstract

Embryo polarization is critical for mouse development; however, neither the regulatory clock nor the molecular trigger that it activates is known. Here, we show that the embryo polarization clock reflects the onset of zygotic genome activation, and we identify three factors required to trigger polarization. Advancing the timing of transcription factor AP-2 gamma (Tfap2c) and TEA domain transcription factor 4 (Tead4) expression in the presence of activated Ras homolog family member A (RhoA) induces precocious polarization as well as subsequent cell fate specification and morphogenesis. Tfap2c and Tead4 induce expression of actin regulators that control the recruitment of apical proteins on the membrane, whereas RhoA regulates their lateral mobility, allowing the emergence of the apical domain. Thus, Tfap2c, Tead4, and RhoA are regulators for the onset of polarization and cell fate segregation in the mouse.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1126/science.abd2703DOIArticle
https://science.sciencemag.org/content/370/6522/eabd2703/suppl/DC1PublisherSupporting Information
https://jakesorel.github.io/Apical_Domain_2020/Related ItemCode
ORCID:
AuthorORCID
Zhu, Meng0000-0001-6157-8840
Cornwall-Scoones, Jake0000-0002-7435-486X
Na, Jie0000-0003-1820-0548
Zernicka-Goetz, Magdalena0000-0002-7004-2471
Additional Information:© 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works https://www.sciencemag.org/about/science-licenses-journal-article-reuse. This is an article distributed under the terms of the Science Journals Default License. Received for publication June 10, 2020. Accepted for publication October 14, 2020. We thank E. Munro, D. Glover, A. Andersen, and M. Shahbazi for helpful discussion; S. Shadkhoo for comments on the model; and S. Malas for the Gata3-GFP transgenic line. Some of the computations were conducted on the Caltech High Performance Cluster, supported by a Gordon and Betty Moore Foundation grant. This work was supported by grants from the Wellcome Trust (098287/Z/12/Z), ERC (669198), Leverhulme Trust (RPG-2018-085), Open Philanthropy/Silicon Valley, Weston Havens Foundations and NIH R01 HD100456-01A1 to M.Z.-G; Packard Foundation, Heritage Medical Research Institute, NIH U01CA244109 to M.T.; and the National Key R&D Program of China grants 2017YFA0102802 and 2019YFA0110001 to J.N. Author contributions: Conceptualization: M.Z. and M.Z.-G. Investigation: M.Z., J.C.-S., P.W., and C.E.H. Writing: M.Z. and M.Z.-G. Supervision: M.Z.-G., M.T., and J.N. The authors declare no competing interests. Data and materials availability: All raw data are available upon request from the corresponding author. The RNA-seq data have been deposited in the Gene Expression Omnibus database (accession number GSE124755). The code for computation simulation has been deposited at https://jakesorel.github.io/Apical_Domain_2020/.
Group:Heritage Medical Research Institute
Funders:
Funding AgencyGrant Number
Gordon and Betty Moore FoundationUNSPECIFIED
Wellcome Trust098287/Z/12/Z
European Research Council (ERC)669198
Leverhulme TrustRPG-2018-085
Open PhilanthropyUNSPECIFIED
Weston Havens FoundationUNSPECIFIED
NIHR01 HD100456-01A1
David and Lucile Packard FoundationUNSPECIFIED
Heritage Medical Research InstituteUNSPECIFIED
NIHU01CA244109
National Key Research and Development Program of China2017YFA0102802
National Key Research and Development Program of China2019YFA0110001
Shurl and Kay Curci FoundationUNSPECIFIED
Issue or Number:6522
Record Number:CaltechAUTHORS:20201210-161600958
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20201210-161600958
Official Citation:Developmental clock and mechanism of de novo polarization of the mouse embryo. BY MENG ZHU, JAKE CORNWALL-SCOONES, PEIZHE WANG, CHARLOTTE E. HANDFORD, JIE NA, MATT THOMSON, MAGDALENA ZERNICKA-GOETZ. Science 11 Dec 2020: Vol. 370, Issue 6522, eabd2703 DOI: 10.1126/science.abd2703
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:107032
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:11 Dec 2020 15:16
Last Modified:11 Dec 2020 15:16

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