Developmental clock and mechanism of de novo polarization of the mouse embryo
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.
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/.Attached Files
Accepted Version - nihms-1714014.pdf
Submitted - 2020.02.10.942201v1.full.pdf
Supplemental Material - abd2703_MDAR_Reproducibility_Checklist.pdf
Supplemental Material - abd2703_Zhu_SM.pdf
Supplemental Material - abd2703s1.mov
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Supplemental Material - abd2703s8.mov
Supplemental Material - abd2703s9.mov
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Additional details
- Alternative title
- Transcriptional control of apical protein clustering drives de novo cell polarity establishment in the early mouse embryo
- PMCID
- PMC8210885
- Eprint ID
- 101233
- Resolver ID
- CaltechAUTHORS:20200212-084819179
- Gordon and Betty Moore Foundation
- 098287/Z/12/Z
- Wellcome Trust
- 669198
- European Research Council (ERC)
- RPG-2018-085
- Leverhulme Trust
- Open Philanthropy
- Weston Havens Foundation
- R01 HD100456-01A1
- NIH
- David and Lucile Packard Foundation
- Heritage Medical Research Institute
- U01CA244109
- NIH
- 2017YFA0102802
- National Key Research and Development Program of China
- 2019YFA0110001
- National Key Research and Development Program of China
- Created
-
2020-02-12Created from EPrint's datestamp field
- Updated
-
2023-07-18Created from EPrint's last_modified field
- Caltech groups
- Division of Biology and Biological Engineering, Division of Biology and Biological Engineering