Human embryo polarization requires PLC signaling to mediate trophectoderm specification.
Mandelbaum, Rachel S
Paulson, Richard J
Mole, Matteo A
Scott, Richard T
de Los Santos, Maria J
eLife Sciences Publications, Ltd
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Zhu, M., Shahbazi, M., Martin, A., Zhang, C., Sozen, B., Borsos, M., Mandelbaum, R. S., et al. (2021). Human embryo polarization requires PLC signaling to mediate trophectoderm specification.. Elife, 10 https://doi.org/10.7554/eLife.65068
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.
Wellcome Trust (WT): Magdalena Zernicka-Goetz, 207415/Z/17/Z; Open Philanthropy Project: Magdalena Zernicka-Goetz; Curci and Weston Heavens Foundations: Magdalena Zernicka-Goetz; Leverhulme Trust: Meng Zhu, RPG-2018-085; European molecular biology organisation: Marta Shahbazi; UKRI | Medical Research Council (MRC): Marta Shahbazi, MC_UP_1201/24; MOST | National Key Research and Development Program of China (973 Program): Zijiang Chen, 2018YFC1004000; Shandong Provincial Key Research and Development Program: Zijiang Chen, 2018YFJH0504 The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Wellcome Trust (207415/Z/17/Z)
External DOI: https://doi.org/10.7554/eLife.65068
This record's URL: https://www.repository.cam.ac.uk/handle/1810/329964
Attribution 4.0 International
Licence URL: https://creativecommons.org/licenses/by/4.0/