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; MRC Laboratory of Molecular Biology. Francis Crick Avenue, Biomedical Campus., Cambridge, United Kingdom
Angel Martin
IVIRMA Valencia, IVI Foundation, Valencia, Spain
Chuanxin Zhang
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
Berna Sozen
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
Mate Borsos
California Institute of Technology, Division of Biology and Biological Engineering,, Pasadena, United States
Rachel S Mandelbaum
USC Fertility, University of Southern California, Keck School of Medicine, Los Angeles, United Kingdom
Richard J Paulson
USC Fertility, University of Southern California, Keck School of Medicine, Los Angeles, United Kingdom
Matteo A Mole
Mammalian Embryo and Stem Cell Group, University of Cambridge, Department of Physiology, Development and Neuroscience, Cambridge, United Kingdom
Marga Esbert
IVIRMA New Jersey, Basking Ridge, NJ, United States
Shiny Titus
IVIRMA New Jersey, Basking Ridge, NJ, United States
Richard T Scott
IVIRMA New Jersey, Basking Ridge, NJ, United States
Alison Campbell
CARE Fertility Group, John Webster House, 6 Lawrence Drive, Nottingham Business Park, Nottingham, United Kingdom
Simon Fishel
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
MRC Laboratory of Molecular Biology. Francis Crick Avenue, Biomedical Campus., Cambridge, United Kingdom
Han Zhao
Key laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, China
Keliang Wu
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
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
IVIRMA New Jersey, Basking Ridge, NJ, United States; Yale School of Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences, New Haven, CT, 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
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.
