Hypoxia affects muscle cell differentiation : the translational repressor 4E‐BP plays a key role

Abstract only The availability of oxygen influences cell growth, proliferation, differentiation and survival. The lack of oxygen affects embryonic cells and molecular mechanisms involved are still unknown. We observed that hypoxia rapidly leads to developmental delay and increase of cell apoptosis after a long term hypoxia exposure during Xenopus embryogenesis. Incubating embryos in hypoxia decreased AKT phosphorylation, reversibly increased embryos lethality and protein level of the translational repressor 4E‐BP. Muscle cell differentiation analyses indicated that hypoxia did not alter somitogenesis but affected proliferation and differentiation without modifying the protein level of MyoD and MRF4 transcription factors. Moreover, the accumulation of the non‐phosphorylatable 4E‐BP protein induced muscle differentiation damage similar to hypoxia conditions. These studies suggest that 4E‐BP protein plays a key role in hypoxia, promoting the cap‐independent translation and specific defects in muscle differentiation.