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Published September 27, 2021 | Supplemental Material + Submitted + Published
Journal Article Open

Human embryo polarization requires PLC signaling to mediate trophectoderm specification


Apico-basal polarization of cells within the embryo is critical for the segregation of distinct lineages during mammalian development. Polarized cells become the trophectoderm (TE), which forms the placenta, and apolar cells become the inner cell mass (ICM), the founding population of the fetus. The cellular and molecular mechanisms leading to polarization of the human embryo and its timing during embryogenesis have remained unknown. Here, we show that human embryo polarization occurs in two steps: it begins with the apical enrichment of F-actin and is followed by the apical accumulation of the PAR complex. This two-step polarization process leads to the formation of an apical domain at the 8–16 cell stage. Using RNA interference, we show that apical domain formation requires Phospholipase C (PLC) signaling, specifically the enzymes PLCB1 and PLCE1, from the eight-cell stage onwards. Finally, we show that although expression of the critical TE differentiation marker GATA3 can be initiated independently of embryo polarization, downregulation of PLCB1 and PLCE1 decreases GATA3 expression through a reduction in the number of polarized cells. Therefore, apical domain formation reinforces a TE fate. The results we present here demonstrate how polarization is triggered to regulate the first lineage segregation in human embryos.

Additional Information

© 2021, Zhu et al. This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited. Received: 20 November 2020; Accepted: 25 September 2021; Published: 27 September 2021. We are thankful to David Glover for comments on the manuscript, Marta Perez Sanchez, Antonia Weberling, Bailey Weatherbee, and Ali Ahmady for the help with human embryo culture, and to USC Fertility and HCLD for their support. M.Z. is funded by Leverhulme Trust. M.N.S. is funded by the European Molecular Biology Organization (EMBO) and the Medical Research Council (MRC, MC_UP_1201/24). Work in the laboratory of M.Z-G. on human embryos is funded by Wellcome Trust (207415/Z/17/Z), Open Philanthropy Grant, Curci, and Weston Havens Foundations. Work in the laboratory of Zi-Jiang Chen is funded by The National Key Research and Development Program of China (2018YFC1004000) and Shandong Provincial Key Research and Development Program (2018YFJH0504). The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. Author contributions: Meng Zhu, Marta Shahbazi, Formal analysis, Investigation, Methodology, Validation, Visualization, Writing – original draft, Writing – review and editing; Angel Martin, Formal analysis, Investigation, Methodology, Validation, Visualization; Chuanxin Zhang, Berna Sozen, Mate Borsos, Marga Esbert, Shiny Titus, Investigation, Validation; Rachel S Mandelbaum, Investigation; Richard J Paulson, Resources, Supervision; Matteo A Mole, Investigation, Visualization; Richard T Scott, Alison Campbell, Simon Fishel, Keliang Wu, Resources; Viviana Gradinaru, Funding acquisition, Supervision; Han Zhao, Zi-Jiang Chen, Funding acquisition, Resources, Supervision; Emre Seli, Conceptualization, Funding acquisition, Resources, Supervision; Maria J de los Santos, Conceptualization, Formal analysis, Funding acquisition, Investigation, Methodology, Resources, Supervision; Magdalena Zernicka Goetz, Conceptualization, Funding acquisition, Methodology, Resources, Supervision, Writing – original draft, Writing – review and editing. Data availability: Source data files used for generating each figure has been uploaded as supplementary material.

Attached Files

Published - elife-65068-v2.pdf

Submitted - 2020.09.23.310680v1.full.pdf

Supplemental Material - elife-65068-supp-v1.zip

Supplemental Material - elife-65068-transrepform1-v2.pdf


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August 20, 2023
December 22, 2023