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Here, we show that SF3B1, a core component of the spliceosome, is upregulated from the 4\u2010cell stage and mediates highly dynamic splicing programs. Depletion of SF3B1 results in developmental arrest at the morula stage, accompanied by widespread transcriptomic dysregulation characterized by aberrant expression of transcription factors that impede pluripotency transition. Alternative splicing analysis further identifies that aberrantly spliced transcripts were significantly enriched in genes involved in cell cycle regulation, such as\n                    <jats:italic>Cdk11b<\/jats:italic>\n                    and\n                    <jats:italic>Ccnb1<\/jats:italic>\n                    . Importantly, we demonstrate that SF3B1 undergoes intrinsic, IDR\u2010driven liquid\u2010liquid phase separation both in vitro and in vivo, forming nuclear condensates in oocytes and early embryos, which is essential for successful development to the blastocyst stage. Together, our findings reveal that phase separation mediated SF3B1 splicing activity is a critical regulator of early mouse embryonic development.\n                  <\/jats:p>","DOI":"10.1002\/advs.77605","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T04:39:14Z","timestamp":1788928754000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Phase Separation of SF3B1 Serves as a Critical Post\u2010Transcriptional Regulator During Early Mouse Embryogenesis"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5621-3564","authenticated-orcid":false,"given":"Kang","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Shanxi Key Laboratory of Birth Defect and Cell Regeneration Shanxi Medical University  Taiyuan China"},{"name":"Key Laboratory of Coal Environmental Pathogenicity and Prevention (Shanxi Medical 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