PDGF signaling in primitive endoderm cell survival is mediated by PI3K-mTOR through p53-independent mechanism

Abstract : Receptor tyrosine kinase signaling (RTK) are key regulators of the formation of the primitive endoderm (PrE) and the epiblast (Epi) from the inner cell mass of the mouse preimplantation embryo. Among them, FGF signaling is critical for PrE cell specification while PDGF signaling is critical for the survival of committed PrE cells. Here, we investigated possible functional redundancies between FGF, PDGF and KIT signaling and showed that only PDGF signaling is involved in PrE cell survival. In addition, we analyzed the effectors downstream of PDGFRα. Our results suggest that the role of PDGF signaling in PrE cell survival is mediated through PI3K-mTOR and independently from p53. Lastly, we uncovered a role for PI3K-mTOR signaling in the survival of Epi cells. Taken together, we propose that survival of ICM cell lineages relies on the regulation of PI3K-mTOR signaling through the regulation of multiple signaling pathways. SIGNIFICANCE STATEMENT: Segregation between embryonic and extra-embryonic lineages occurs at the beginning of mammalian development and requires multiple processes participating in the acquisition and the maintenance of cell identities. In this study, we have characterized the intracellular factors involved in the survival of the epiblast, that will form the embryo proper, and the primitive endoderm, an extraembryonic lineage participating to the formation of the yolk sac, just after their formation. Such better understanding of early embryonic development could benefit to the fields of stem cell biology and assisted reproduction technologies. © AlphaMed Press 2019.