AbstractThe conserved 3’-5’ exoribonuclease EXOSC10/Rrp6 is required for gametogenesis, brain development, erythropoiesis and blood cell enhancer function. The human ortholog is essential for mitosis in cultured cancer cells. Little is known, however, about the role ofExosc10during embryo development and organogenesis. We generated anExosc10knockout model and find thatExosc10−/−mice show an embryonic lethal phenotype. We demonstrate thatExosc10maternal wild type mRNA is present in mutant oocytes and that the gene is expressed during all stages of early embryogenesis. Furthermore, we observe that EXOSC10 early on localizes to the periphery of nucleolus precursor bodies in blastomeres, which is in keeping with the protein’s role in rRNA processing and may indicate a function in the establishment of chromatin domains during initial stages of embryogenesis. Finally, we infer from genotyping data for embryonic days e7.5, e6.5 and e4.5 and embryos culturedin vitrothatExosc10−/−mutants arrest at the eight-cell embryo/morula transition. Our results demonstrate a novel essential role forExosc10during early embryogenesis, and they are consistent with earlier work showing that impaired ribosome biogenesis causes a developmental arrest at the morula stage.