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A conserved role of the Hippo signalling pathway in initiation of the first lineage specification event across mammals

Gerri, C; McCarthy, A; Scott, GM; Regin, M; Stamatiadis, P; Brumm, S; Simon, CS; Lee, J; Montesinos, C; Hassitt, C; Hockenhull, S; Hampshire, D; Elder, K; Snell, P; Christie, L; Fouladi-Nashta, AA; Van de Velde, H; Niakan, KK

Authors

C Gerri

A McCarthy

GM Scott

M Regin

P Stamatiadis

S Brumm

CS Simon

J Lee

C Montesinos

C Hassitt

S Hockenhull

D Hampshire

K Elder

P Snell

L Christie

AA Fouladi-Nashta

H Van de Velde

KK Niakan



Abstract

Our understanding of the molecular events driving cell specification in early mammalian development relies mainly on mouse studies, and it remains unclear whether these mechanisms are conserved across mammals, including humans. We have shown that the establishment of cell polarity via aPKC is a conserved event in the initiation of the trophectoderm (TE) placental programme in mouse, cow and human embryos. However, the mechanisms transducing cell polarity into cell fate in cow and human embryos are unknown. Here, we have examined the evolutionary conservation of Hippo signalling, which is thought to function downstream of aPKC activity, in four different mammalian species: mouse, rat, cow and human. In all four species, inhibition of the Hippo pathway by targeting LATS kinases is sufficient to drive ectopic TE initiation and downregulation of SOX2. However, the timing and localisation of molecular markers differ across species, with rat embryos more closely recapitulating human and cow developmental dynamics, compared with the mouse. Our comparative embryology approach uncovered intriguing differences as well as similarities in a fundamental developmental process among mammals, reinforcing the importance of cross-species investigations.

Citation

Gerri, C., McCarthy, A., Scott, G., Regin, M., Stamatiadis, P., Brumm, S., …Niakan, K. (2023). A conserved role of the Hippo signalling pathway in initiation of the first lineage specification event across mammals. Development, 150(8), https://doi.org/10.1242/dev.201112

Journal Article Type Article
Acceptance Date Mar 6, 2023
Online Publication Date Apr 20, 2023
Publication Date 2023
Deposit Date Jun 19, 2024
Print ISSN 1011-6370
Publisher The Company of Biologists
Peer Reviewed Peer Reviewed
Volume 150
Issue 8
DOI https://doi.org/10.1242/dev.201112
Keywords Comparative embryology; Early development; Hippo signalling pathway; Human; Lineage specification; Placental programme; MOUSE EMBRYO; PREIMPLANTATION; TROPHECTODERM; EXPRESSION; CELLS; LOCALIZATION; CYCLES; TEAD4; CDX2
Publisher URL https://journals.biologists.com/dev/article/150/8/dev201112/307115/A-conserved-role-of-the-Hippo-signalling-pathway