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

Anna Geiselmann (1, 2, 3) , Adèle Micouin (1, 3, 4) , Sandrine Vandormael-Pournin (1, 3) , Vincent Laville (5) , Sébastien Mella (6) , Pablo Navarro (1) , Michel Cohen-Tannoudji (1, 3)

1 EPIC - Epigénomique, Prolifération et Identité Cellulaire - Epigenomics, Proliferation and the Identity of Cells
2 ED515 - Ecole Doctorale Complexité du Vivant
3 Embryon précoce de mammifères et cellules souches - Early Mammalian Development & Stem Cell Biology
4 ED562 - BioSPC - École Doctorale Bio Sorbonne Paris Cité [Paris]
5 Département de Biologie du Développement et Cellules souches - Department of Developmental and Stem Cell Biology
6 Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB

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.

Mots clés: mTOR; Mouse preimplantation embryo; Epiblast; Primitive endoderm; Inner cell mass; Lineage specification; NANOG; GSK3; FOXO3

Domaines: Sciences du Vivant [q-bio]; Biologie du développement

Anna Geiselmann, Adèle Micouin, Sandrine Vandormael-Pournin, Vincent Laville, Sébastien Mella, et al.. PI3K/AKT signalling orchestrates ICM maturation and proper epiblast and primitive endoderm specification. 2023. ⟨pasteur-04228611⟩