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
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.
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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/. | ||||||||||||||||||||||||||
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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 | ||||||||||||||||||||||||||
Usage Policy: | No commercial reproduction, distribution, display or performance rights in this work are provided. | ||||||||||||||||||||||||||
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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