Human embryo polarization requires PLC signaling to mediate trophectoderm specification

eLife

Alison Campbell¹  Simon Fishel²  Mate Borsos³  Keliang Wu⁴  Chuanxin Zhang⁴  Zi-Jiang Chen⁴  Berna Sozen⁵  Richard T Scott⁶  Shiny Titus⁶  Marga Esbert⁶  Emre Seli⁷  Angel Martin⁸  Maria J de los Santos⁸  Han Zhao⁹  Viviana Gradinaru^1,10  Matteo A Mole^1,11  Meng Zhu^1,12  Magdalena Zernicka Goetz^1,13  Marta Shahbazi^1,14  Rachel S Mandelbaum^1,15  Richard J Paulson^1,15 

[1] CARE Fertility Group, John Webster House, 6 Lawrence Drive, Nottingham Business Park, Nottingham, United Kingdom;CARE Fertility Group, John Webster House, 6 Lawrence Drive, Nottingham Business Park, Nottingham, United Kingdom;School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, United Kingdom;California Institute of Technology, Division of Biology and Biological Engineering,, Pasadena, United States;Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan, China;Key laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, China;Developmental Plasticity and Self-Organization Group, California Institute of Technology, Division of Biology and Biological Engineering, Pasadena, United States;Yale School of Medicine, Department of Genetics, New Haven, CT, United States;IVIRMA New Jersey, Basking Ridge, NJ, United States;IVIRMA New Jersey, Basking Ridge, NJ, United States;Yale School of Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences, New Haven, CT, United States;IVIRMA Valencia, IVI Foundation, Valencia, Spain;Key laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, China;MRC Laboratory of Molecular Biology. Francis Crick Avenue, Biomedical Campus., Cambridge, United Kingdom;Mammalian Embryo and Stem Cell Group, University of Cambridge, Department of Physiology, Development and Neuroscience, Cambridge, United Kingdom;Mammalian Embryo and Stem Cell Group, University of Cambridge, Department of Physiology, Development and Neuroscience, Cambridge, United Kingdom;Blavatnik Institute, Harvard Medical School, Department of Genetics, Boston, United States;Mammalian Embryo and Stem Cell Group, University of Cambridge, Department of Physiology, Development and Neuroscience, Cambridge, United Kingdom;Developmental Plasticity and Self-Organization Group, California Institute of Technology, Division of Biology and Biological Engineering, Pasadena, United States;Mammalian Embryo and Stem Cell Group, University of Cambridge, Department of Physiology, Development and Neuroscience, Cambridge, United Kingdom;MRC Laboratory of Molecular Biology. Francis Crick Avenue, Biomedical Campus., Cambridge, United Kingdom;USC Fertility, University of Southern California, Keck School of Medicine, Los Angeles, United Kingdom;

关键词: human embryo;    cell polarity;    preimplantation;    Other;   

DOI  :  10.7554/eLife.65068

来源: eLife Sciences Publications, Ltd

【 摘 要 】

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.

【 授权许可】

CC BY