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

Gerri, C and McCarthy, A and Alanis-Lobato, G and Demtschenko, A and Bruneau, A and Loubersac, S and Fogarty, N M E and Hampshire, D and Elder, K and Snell, P and Christie, L and David, L and Van de Velde, H and Fouladi-Nashta, A A and Niakan, K K (2020) Initiation of a conserved trophectoderm program in human, cow and mouse embryos. Nature. ISSN 0028-0836

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Official URL: https://doi.org/10.1038/s41586-020-2759-x

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 human2,3,4,5 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.

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