Apicobasal RNA asymmetries regulate cell fate in the early mouse embryo

Azelle Hawdon, Niall D. Geoghegan, Monika Mohenska, Anja Elsenhans, Charles Ferguson, Jose M. Polo, Robert G. Parton, Jennifer Zenker

Research output: Contribution to journalArticleResearchpeer-review

6 Citations (Scopus)


The spatial sorting of RNA transcripts is fundamental for the refinement of gene expression to distinct subcellular regions. Although, in non-mammalian early embryogenesis, differential RNA localisation presages cell fate determination, in mammals it remains unclear. Here, we uncover apical-to-basal RNA asymmetries in outer blastomeres of 16-cell stage mouse preimplantation embryos. Basally directed RNA transport is facilitated in a microtubule- and lysosome-mediated manner. Yet, despite an increased accumulation of RNA transcripts in basal regions, higher translation activity occurs at the more dispersed apical RNA foci, demonstrated by spatial heterogeneities in RNA subtypes, RNA-organelle interactions and translation events. During the transition to the 32-cell stage, the biased inheritance of RNA transcripts, coupled with differential translation capacity, regulates cell fate allocation of trophectoderm and cells destined to form the pluripotent inner cell mass. Our study identifies a paradigm for the spatiotemporal regulation of post-transcriptional gene expression governing mammalian preimplantation embryogenesis and cell fate.

Original languageEnglish
Article number2909
Number of pages30
JournalNature Communications
Issue number1
Publication statusPublished - Dec 2023

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