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...
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eLife Sciences Publications Ltd
2021
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oai:doaj.org-article:579ed260e0bd4dd89e8d938ef11881a92021-11-15T05:40:04ZHuman embryo polarization requires PLC signaling to mediate trophectoderm specification10.7554/eLife.650682050-084Xe65068https://doaj.org/article/579ed260e0bd4dd89e8d938ef11881a92021-09-01T00:00:00Zhttps://elifesciences.org/articles/65068https://doaj.org/toc/2050-084XApico-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.Meng ZhuMarta ShahbaziAngel MartinChuanxin ZhangBerna SozenMate BorsosRachel S MandelbaumRichard J PaulsonMatteo A MoleMarga EsbertShiny TitusRichard T ScottAlison CampbellSimon FishelViviana GradinaruHan ZhaoKeliang WuZi-Jiang ChenEmre SeliMaria J de los SantosMagdalena Zernicka GoetzeLife Sciences Publications Ltdarticlehuman embryocell polaritypreimplantationMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021) |
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DOAJ |
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DOAJ |
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EN |
| topic |
human embryo cell polarity preimplantation Medicine R Science Q Biology (General) QH301-705.5 |
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human embryo cell polarity preimplantation Medicine R Science Q Biology (General) QH301-705.5 Meng Zhu Marta Shahbazi Angel Martin Chuanxin Zhang Berna Sozen Mate Borsos Rachel S Mandelbaum Richard J Paulson Matteo A Mole Marga Esbert Shiny Titus Richard T Scott Alison Campbell Simon Fishel Viviana Gradinaru Han Zhao Keliang Wu Zi-Jiang Chen Emre Seli Maria J de los Santos Magdalena Zernicka Goetz Human embryo polarization requires PLC signaling to mediate trophectoderm specification |
| description |
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. |
| format |
article |
| author |
Meng Zhu Marta Shahbazi Angel Martin Chuanxin Zhang Berna Sozen Mate Borsos Rachel S Mandelbaum Richard J Paulson Matteo A Mole Marga Esbert Shiny Titus Richard T Scott Alison Campbell Simon Fishel Viviana Gradinaru Han Zhao Keliang Wu Zi-Jiang Chen Emre Seli Maria J de los Santos Magdalena Zernicka Goetz |
| author_facet |
Meng Zhu Marta Shahbazi Angel Martin Chuanxin Zhang Berna Sozen Mate Borsos Rachel S Mandelbaum Richard J Paulson Matteo A Mole Marga Esbert Shiny Titus Richard T Scott Alison Campbell Simon Fishel Viviana Gradinaru Han Zhao Keliang Wu Zi-Jiang Chen Emre Seli Maria J de los Santos Magdalena Zernicka Goetz |
| author_sort |
Meng Zhu |
| title |
Human embryo polarization requires PLC signaling to mediate trophectoderm specification |
| title_short |
Human embryo polarization requires PLC signaling to mediate trophectoderm specification |
| title_full |
Human embryo polarization requires PLC signaling to mediate trophectoderm specification |
| title_fullStr |
Human embryo polarization requires PLC signaling to mediate trophectoderm specification |
| title_full_unstemmed |
Human embryo polarization requires PLC signaling to mediate trophectoderm specification |
| title_sort |
human embryo polarization requires plc signaling to mediate trophectoderm specification |
| publisher |
eLife Sciences Publications Ltd |
| publishDate |
2021 |
| url |
https://doaj.org/article/579ed260e0bd4dd89e8d938ef11881a9 |
| work_keys_str_mv |
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1718428552914796544 |