KRAS is required for placenta development

Besides its well-known roles in cancer, KRAS is important for embryogenesis, as its absence causes embryonic lethality. The precise mechanisms underlying the developmental functions of KRAS is still incompletely characterized. To address this issue, we analyzed Kras-/- mouse embryos. We observed that Kras-/- embryos show a lethality that starts around E13.5. Interestingly, a placental phenotype was observed in Kras-/- embryos. This phenotype was associated with a small placental size, and a marked decrease in glycogen trophoblast cells. It was related to the presence of hypoglycaemia and hypoxia in Kras-/- embryos. Thus, our study reveals hidden functions of KRAS4. Importantly, it identifies for the first time a role for KRAS in the differentiation process of a specific cell type and the biological defects caused by a loss of KRAS. Overall design: Wild-type and Kras-/- mouse placenta were collected at e13.5. Cell nuclei were purified, RNA was extracted and submitted to snRNAseq.