{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T10:52:55Z","timestamp":1791975175301,"version":"4.4.0"},"reference-count":0,"publisher":"The Company of Biologists","license":[{"start":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:00:00Z","timestamp":1791936000000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","award":["R01 HD108722"],"award-info":[{"award-number":["R01 HD108722"]}],"id":[{"id":"https:\/\/ror.org\/04byxyr05","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>In mammals, the first cell fate decisions segregate pluripotent fetal cells from the differentiating extraembryonic lineages. In mouse, pluripotent progenitors can be identified as early as the 16-cell (morula) stage, based on their restricted expression of SOX2. In spite of the unique SOX2 expression pattern, however, the first cell fate decision proceeds normally in the absence of Sox2, suggesting an undiscovered compensatory mechanism. We discovered that the closely related Sox paralogue SOX21 is expressed alongside, and independently of Sox2 prior to blastocyst formation. Embryos lacking both Sox2 and Sox21 exhibit a phenotype more severe than those lacking either gene alone, arresting during the morula-to-blastocyst transition. In fact, embryos lacking any three copies of Sox2 or Sox21 frequently phenocopy double knockouts, consistent with a dose-dependent genetic interaction. Finally, we discovered the mechanism promoting parallel expression of Sox2 and Sox21. We show that, like Sox2, expression of Sox21 depends on TFAP2C, and not NANOG or OCT4, clarifying gene regulatory mechanisms preceding blastocyst formation. Overall, our study reveals a novel Sox-dependent pathway regulating embryonic processes even earlier than previously appreciated.<\/jats:p>","DOI":"10.1242\/dev.205635","type":"journal-article","created":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T10:29:41Z","timestamp":1791973781000},"source":"Crossref","is-referenced-by-count":0,"title":["SOX21 and SOX2 collaboratively promote blastocyst formation downstream of TFAP2C"],"prefix":"10.1242","author":[{"given":"Farina","family":"Aziz","sequence":"first","affiliation":[{"name":"1 Cell and Molecular Biology Graduate Program, Michigan State University, East Lansing, MI, 48824, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiera","family":"Savage","sequence":"additional","affiliation":[{"name":"1 Cell and Molecular Biology Graduate Program, Michigan State University, East Lansing, MI, 48824, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaehwan","family":"Kim","sequence":"additional","affiliation":[{"name":"2 Department of Animal Science, Michigan State University, East Lansing, MI, 48824, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason G.","family":"Knott","sequence":"additional","affiliation":[{"name":"2 Department of Animal Science, Michigan State University, East Lansing, MI, 48824, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Gu","sequence":"additional","affiliation":[{"name":"3 Department of Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, East Lansing, MI, 48824, USA"},{"name":"4 Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI, 48824, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Halbisen","sequence":"additional","affiliation":[{"name":"5 Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI, 48824, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3755-8262","authenticated-orcid":false,"given":"Amy","family":"Ralston","sequence":"additional","affiliation":[{"name":"5 Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI, 48824, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2026,10,14]]},"container-title":["Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.biologists.com\/dev\/article-pdf\/doi\/10.1242\/dev.205635\/3721368\/dev205635.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/journals.biologists.com\/dev\/article-pdf\/doi\/10.1242\/dev.205635\/3721368\/dev205635.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T10:29:41Z","timestamp":1791973781000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.biologists.com\/dev\/article\/doi\/10.1242\/dev.205635\/373167\/SOX21-and-SOX2-collaboratively-promote-blastocyst"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,14]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1242\/dev.205635","relation":{},"ISSN":["0950-1991","1477-9129"],"issn-type":[{"value":"0950-1991","type":"print"},{"value":"1477-9129","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,14]]},"article-number":"dev.205635"}}