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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


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


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.


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,

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
Public URL
Publisher URL


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