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© Research
Publication :

PI3K/AKT signalling orchestrates ICM maturation and proper epiblast and primitive endoderm specification

Team: Early Mammalian Development & Stem Cell Biology
Team: Epigenomics, Proliferation and the Identity of Cells – EPIC
Member: Michel Cohen-Tannoudji
Scientific Fields
Diseases
Organisms
Applications
Technique

Published in - 21 Jun 2023

Anna Geiselmann, Adèle Micouin, Sandrine Vandormael-Pournin, Vincent Laville, Sébastien Mella, Pablo Navarro, Michel Cohen-Tannoudji

Link to HAL – pasteur-04228611

Link to DOI – 10.1101/2023.06.21.545867

2023

The inner cell mass (ICM) of early mouse embryos is specified into Epiblast (Epi) and primitive endoderm (PrE) lineages during blastocyst formation. The antagonistic transcription factors (TFs) NANOG and GATA6 in combination with FGF/ERK signalling are central actors in ICM fate choice. However, what initiates the specification of ICM progenitors and whether other factors are involved in this process is not fully understood yet. Here, we show that PI3K/AKT is constitutively active during preimplantation development. Using pharmacological inhibition, we demonstrate that PI3K/AKT enables the formation of a functional ICM capable of giving rise to both the EPI and the PrE: it maintains the expression of the TF NANOG, which specifies the EPI, and confers responsiveness to FGF4, which is essential for PrE specification. Our observations thus identify PI3K/AKT signalling as an upstream regulator orchestrating the molecular events required for both EPI and PrE specification.