Initiation of a conserved trophectoderm program in human, cow and mouse embryos

Claudia Gerri, Afshan McCarthy, Gregorio Alanis-Lobato, Andrej Demtschenko, Alexandre Bruneau, Sophie Loubersac, Norah M. E. Fogarty, Daniel Hampshire, Kay Elder, Phil Snell, Leila Christie, Laurent David, Hilde Van de Velde, Ali A. Fouladi-Nashta and Kathy K. Niakan ()
Additional contact information
Claudia Gerri: The Francis Crick Institute
Afshan McCarthy: The Francis Crick Institute
Gregorio Alanis-Lobato: The Francis Crick Institute
Andrej Demtschenko: Vrije Universiteit Brussel
Alexandre Bruneau: Université de Nantes, CHU Nantes, Inserm, Centre de Recherche en Transplantation et Immunologie, UMR 1064, ITUN
Sophie Loubersac: Université de Nantes, CHU Nantes, Inserm, Centre de Recherche en Transplantation et Immunologie, UMR 1064, ITUN
Norah M. E. Fogarty: The Francis Crick Institute
Daniel Hampshire: Royal Veterinary College
Kay Elder: Bourn Hall Clinic
Phil Snell: Bourn Hall Clinic
Leila Christie: Bourn Hall Clinic
Laurent David: Université de Nantes, CHU Nantes, Inserm, Centre de Recherche en Transplantation et Immunologie, UMR 1064, ITUN
Hilde Van de Velde: Vrije Universiteit Brussel
Ali A. Fouladi-Nashta: Royal Veterinary College
Kathy K. Niakan: The Francis Crick Institute

Nature, 2020, vol. 587, issue 7834, 443-447

Abstract: Abstract Current understandings of cell specification in early mammalian pre-implantation development are based mainly on mouse studies. The first lineage differentiation event occurs at the morula stage, with outer cells initiating a trophectoderm (TE) placental progenitor program. The inner cell mass arises from inner cells during subsequent developmental stages and comprises precursor cells of the embryo proper and yolk sac1. Recent gene-expression analyses suggest that the mechanisms that regulate early lineage specification in the mouse may differ in other mammals, including human2–5 and cow6. Here we show the evolutionary conservation of a molecular cascade that initiates TE segregation in human, cow and mouse embryos. At the morula stage, outer cells acquire an apical–basal cell polarity, with expression of atypical protein kinase C (aPKC) at the contact-free domain, nuclear expression of Hippo signalling pathway effectors and restricted expression of TE-associated factors such as GATA3, which suggests initiation of a TE program. Furthermore, we demonstrate that inhibition of aPKC by small-molecule pharmacological modulation or Trim-Away protein depletion impairs TE initiation at the morula stage. Our comparative embryology analysis provides insights into early lineage specification and suggests that a similar mechanism initiates a TE program in human, cow and mouse embryos.

Date: 2020
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DOI: 10.1038/s41586-020-2759-x

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