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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

Authors

C Gerri

A McCarthy

G Alanis-Lobato

A Demtschenko

A Bruneau

S Loubersac

N M E Fogarty

D Hampshire

K Elder

P Snell

L Christie

L David

H Van de Velde

A A Fouladi-Nashta

K K Niakan



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., …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
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

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