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. PMCID PMC8210885. doi:10.1126/science.abd2703. https://resolver.caltech.edu/CaltechAUTHORS:20200212-084819179

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	PDF (Materials and Methods; Supplementary Text; Figs. S1 and S12; Tables S1 to S4; Captions for Movies S1 to S15; References) - Supplemental Material See Usage Policy. 19MB
	PDF (MDAR Reproducibility Checklist) - Supplemental Material See Usage Policy. 101kB
	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 See Usage Policy. 5MB
	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 See Usage Policy. 5MB
	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 See Usage Policy. 2MB
	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 See Usage Policy. 643kB
	Video (QuickTime) (Movie S5. Time-lapse imaging of the membrane disorganization induced by RhoAQ63L overexpression at the late 4-cell stage) - Supplemental Material See Usage Policy. 502kB
	Video (QuickTime) (Movie S6. Time-lapse imaging of the apical domains formation induced by Tead4, Tfap2c and RhoA-Q63L overexpression) - Supplemental Material See Usage Policy. 785kB
	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 See Usage Policy. 10MB
	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 See Usage Policy. 9MB
	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 See Usage Policy. 8MB
	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 See Usage Policy. 3MB
	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 See Usage Policy. 5MB
	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 See Usage Policy. 13MB
	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 See Usage Policy. 10MB
	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 See Usage Policy. 8MB
	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 See Usage Policy. 5MB

Use this Persistent URL to link to this item: https://resolver.caltech.edu/CaltechAUTHORS:20200212-084819179

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:

URL	URL Type	Description
https://doi.org/10.1126/science.abd2703	DOI	Article
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8210885	PubMed Central	Article
https://jakesorel.github.io/Apical_Domain_2020/	Related Item	Code
https://doi.org/10.1101/2020.02.10.942201	DOI	Discussion Paper

ORCID:

Author	ORCID
Zhu, Meng	0000-0001-6157-8840
Cornwall-Scoones, Jake	0000-0002-7435-486X
Na, Jie	0000-0003-1820-0548
Thomson, Matt	0000-0003-1021-1234
Zernicka-Goetz, Magdalena	0000-0002-7004-2471

Alternate Title:

Transcriptional control of apical protein clustering drives de novo cell polarity establishment in the early mouse embryo

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/.

Funders:

Funding Agency	Grant Number
Gordon and Betty Moore Foundation	UNSPECIFIED
Wellcome Trust	098287/Z/12/Z
European Research Council (ERC)	669198
Leverhulme Trust	RPG-2018-085
Open Philanthropy	UNSPECIFIED
Weston Havens Foundation	UNSPECIFIED
NIH	R01 HD100456-01A1
David and Lucile Packard Foundation	UNSPECIFIED
Heritage Medical Research Institute	UNSPECIFIED
NIH	U01CA244109
National Key Research and Development Program of China	2017YFA0102802
National Key Research and Development Program of China	2019YFA0110001

Issue or Number:

6522

PubMed Central ID:

PMC8210885

DOI:

10.1126/science.abd2703

Record Number:

CaltechAUTHORS:20200212-084819179

Persistent URL:

https://resolver.caltech.edu/CaltechAUTHORS:20200212-084819179

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

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ID Code:

101233

Collection:

CaltechAUTHORS

Deposited By:

Tony Diaz

Deposited On:

12 Feb 2020 17:35

Last Modified:

05 Oct 2021 20:12

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