PI3K/AKT signaling controls ICM maturation and proper epiblast and primitive endoderm specification in mice.

Autor:	Geiselmann A; Institut Pasteur, Université Paris Cité, CNRS UMR 3738, Epigenomics, Proliferation, and the Identity of Cells, Department of Developmental and Stem Cell Biology, 75015 Paris, France; Sorbonne Université, Complexité du Vivant, 75005 Paris, France; Institut Pasteur, Université Paris Cité, CNRS UMR3738, Early Mammalian Development and Stem Cell Biology, 75015 Paris, France., Micouin A; Institut Pasteur, Université Paris Cité, CNRS UMR 3738, Epigenomics, Proliferation, and the Identity of Cells, Department of Developmental and Stem Cell Biology, 75015 Paris, France; Institut Pasteur, Université Paris Cité, CNRS UMR3738, Early Mammalian Development and Stem Cell Biology, 75015 Paris, France; Université Paris Cité, BioSPC, 75013 Paris, France., Vandormael-Pournin S; Institut Pasteur, Université Paris Cité, CNRS UMR 3738, Epigenomics, Proliferation, and the Identity of Cells, Department of Developmental and Stem Cell Biology, 75015 Paris, France; Institut Pasteur, Université Paris Cité, CNRS UMR3738, Early Mammalian Development and Stem Cell Biology, 75015 Paris, France., Laville V; Department of Developmental and Stem Cell Biology, Institut Pasteur, CNRS UMR 3738, 75015 Paris, France; Institut Pasteur, Université Paris Cité, Bioinformatics and Biostatistics Hub, 75015 Paris, France., Chervova A; Institut Pasteur, Université Paris Cité, CNRS UMR 3738, Epigenomics, Proliferation, and the Identity of Cells, Department of Developmental and Stem Cell Biology, 75015 Paris, France., Mella S; Institut Pasteur, Université Paris Cité, Bioinformatics and Biostatistics Hub, 75015 Paris, France., Navarro P; Institut Pasteur, Université Paris Cité, CNRS UMR 3738, Epigenomics, Proliferation, and the Identity of Cells, Department of Developmental and Stem Cell Biology, 75015 Paris, France., Cohen-Tannoudji M; Institut Pasteur, Université Paris Cité, CNRS UMR 3738, Epigenomics, Proliferation, and the Identity of Cells, Department of Developmental and Stem Cell Biology, 75015 Paris, France; Institut Pasteur, Université Paris Cité, CNRS UMR3738, Early Mammalian Development and Stem Cell Biology, 75015 Paris, France. Electronic address: m-cohen@pasteur.fr.
Jazyk:	angličtina
Zdroj:	Developmental cell [Dev Cell] 2024 Oct 25. Date of Electronic Publication: 2024 Oct 25.
DOI:	10.1016/j.devcel.2024.10.001
Abstrakt:	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 GATA-binding protein 6 (GATA6) in combination with fibroblast growth factor (FGF)/extracellular-signal-regulated kinase (ERK) signaling are central actors in ICM fate choice. However, what initiates the specification of ICM progenitors into Epi or PrE and whether other factors are involved in this process has not been fully understood yet. Here, we show that phosphoinositide 3-kinase (PI3K)/protein kinase B (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 work thus identifies PI3K/AKT signaling as an upstream regulator controlling the molecular events required for both Epi and PrE specification. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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