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

Gerri, C; McCarthy, A; Alanis-Lobato, G; Demtschenko, A; Bruneau, A; Loubersac, S; Fogarty, N M E; Hampshire, D; Elder, K; Snell, P; Christie, L; David, L; Van de Velde, H; Fouladi-Nashta, A A; Niakan, K K

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.

Citation

Gerri, C., McCarthy, A., Alanis-Lobato, G., Demtschenko, A., Bruneau, A., Loubersac, S., Fogarty, N. M. E., Hampshire, D., Elder, K., Snell, P., Christie, L., David, L., Van de Velde, H., Fouladi-Nashta, A. A., & Niakan, K. K. (2020). Initiation of a conserved trophectoderm program in human, cow and mouse embryos. Nature, https://doi.org/10.1038/s41586-020-2759-x

• Journal Article Type: Article
• Acceptance Date: Aug 21, 2020
• Publication Date: Sep 23, 2020
• Deposit Date: Sep 30, 2020
• Publicly Available Date: Oct 1, 2020
• Journal: Nature
• Print ISSN: 0028-0836
• Electronic ISSN: 1476-4687
• Publisher: Nature Research
• Peer Reviewed: Peer Reviewed
• DOI: https://doi.org/10.1038/s41586-020-2759-x
• Public URL: https://rvc-repository.worktribe.com/output/1375578
• Publisher URL: https://doi.org/10.1038/s41586-020-2759-x