{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T17:06:23Z","timestamp":1790183183191,"version":"4.1.0"},"reference-count":65,"publisher":"National Academy of Sciences","issue":"39","license":[{"start":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"MOST | National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32172962 and U23A20245"],"award-info":[{"award-number":["32172962 and U23A20245"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Fundamental Research Funds for the Central Universities of China","award":["2662025SCPY006"],"award-info":[{"award-number":["2662025SCPY006"]}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,9,29]]},"abstract":"<jats:p>\n                    Polyploidy represents a major driver of eukaryotic genome evolution. In vertebrates, premeiotic endoreplication is considered as an important route to polyploidization, yet the molecular basis governing this process remains elusive. Here, we reported that heterozygous mutation of\n                    <jats:italic toggle=\"yes\">cdk1<\/jats:italic>\n                    in the loach,\n                    <jats:italic toggle=\"yes\">Misgurnus anguillicaudatus<\/jats:italic>\n                    (Teleostei, Cobitidae), triggered premeiotic endoreplication in spermatogonia, resulting in the production of unreduced diploid sperms. Through integrated proteomic and phosphoproteomic profiling, we uncovered that Cdk1 heterozygosity led to widespread dysregulation of the phosphorylation of key proteins in the cell cycle and DNA replication pathways in spermatogonia. Mechanistically, Cdk1 heterozygosity induced increased inhibitory phosphorylation of Cdk2 at tyrosine 15, and accumulated Cdk2\/Ccne1 complex directly phosphorylated Fzr1a at threonine 124, inhibiting APC\/C\n                    <jats:sup>Fzr1a<\/jats:sup>\n                    complex activity. Cdk2 Y15 phosphorylation arrested cells at the G1\/S boundary, while Fzr1a phosphorylation-driven APC\/C\n                    <jats:sup>Fzr1a<\/jats:sup>\n                    inactivation blocked mitotic exit and sustained DNA replication, thereby triggering premeiotic endoreplication. Inhibition of Cdk2 expression in\n                    <jats:italic toggle=\"yes\">cdk1<\/jats:italic>\n                    <jats:sup>+\/\u2212<\/jats:sup>\n                    loach males suppressed this pathway and abolished unreduced sperm formation. Our study elucidates the molecular pathway for unreduced gamete production in fish and establishes Cdk1 as a key guardian of diploidy before meiosis. Furthermore, leveraging this mechanism, we generated triploid and tetraploid loach lines with unreduced sperms, demonstrating a direct bridge between gene function and polyploid breeding. These findings provide a mechanistic framework for understanding polyploidization in vertebrate evolution and offer a targeted strategy for chromosome set manipulation in aquaculture.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2613873123","type":"journal-article","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T16:25:03Z","timestamp":1790180703000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":0,"title":["Cdk1 heterozygosity triggers premeiotic endoreplication and unreduced sperm formation via the Cdk2\/Ccne1\u2013Fzr1a pathway in loach, a teleost"],"prefix":"10.1073","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-1067-2722","authenticated-orcid":false,"given":"Yunbang","family":"Zhang","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/023b72294","id-type":"ROR","asserted-by":"publisher"}],"name":"College of Fisheries, Engineering Research Center of Green Development for Conventional Aquatic Biological Industry in the Yangtze River Economic Belt, Ministry of Education, Huazhong Agricultural University","place":["Wuhan, China"]},{"name":"Ministry of Education Key Laboratory of Freshwater Fish Reproduction and Development, College of Fisheries, Integrative Science Center of Germplasm Creation in Western China (Chongqing) Science City, Southwest University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongyun","family":"Li","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/023b72294","id-type":"ROR","asserted-by":"publisher"}],"name":"College of Fisheries, Engineering Research Center of Green Development for Conventional Aquatic Biological Industry in the Yangtze River Economic Belt, Ministry of Education, Huazhong Agricultural University","place":["Wuhan, China"]},{"name":"Ministry of Education Key Laboratory of Freshwater Fish Reproduction and Development, College of Fisheries, 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Biological Industry in the Yangtze River Economic Belt, Ministry of Education, Huazhong Agricultural University","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Zhang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/023b72294","id-type":"ROR","asserted-by":"publisher"}],"name":"College of Fisheries, Engineering Research Center of Green Development for Conventional Aquatic Biological Industry in the Yangtze River Economic Belt, Ministry of Education, Huazhong Agricultural University","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxuan","family":"Zheng","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/023b72294","id-type":"ROR","asserted-by":"publisher"}],"name":"College of Fisheries, Engineering Research Center of Green Development for Conventional Aquatic Biological Industry in the Yangtze River Economic Belt, Ministry of Education, Huazhong 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Agricultural University","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yankun","family":"Guo","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/023b72294","id-type":"ROR","asserted-by":"publisher"}],"name":"College of Fisheries, Engineering Research Center of Green Development for Conventional Aquatic Biological Industry in the Yangtze River Economic Belt, Ministry of Education, Huazhong Agricultural University","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxin","family":"Jiang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/023b72294","id-type":"ROR","asserted-by":"publisher"}],"name":"College of Fisheries, Engineering Research Center of Green Development for Conventional Aquatic Biological Industry in the Yangtze River Economic Belt, Ministry of Education, Huazhong Agricultural University","place":["Wuhan, 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(Wiley Online Library, 2018), pp. 137\u2013162."},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.200345"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12562-023-01703-8"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/jxb\/erq371"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1000124"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2016.117"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/plcell\/koab178"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-024-01750-6"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/molbev\/msae047"},{"key":"e_1_3_4_17_2","first-page":"547","article-title":"Mei4 deficiency leads to sexual dimorphism of early meiosis and occurrence of unreduced eggs in zebrafish","volume":"47","author":"Miao L. J.","year":"2026","unstructured":"L. J. 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B. Zhang Proteomic and phosphoproteomic analysis of WT and cdk1+\/\u2212 loach. iProX. https:\/\/www.iprox.cn\/\/page\/subproject.html?id=IPX0016687001. Deposited 17 April 2026."}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2613873123","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T16:25:29Z","timestamp":1790180729000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2613873123"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,23]]},"references-count":65,"journal-issue":{"issue":"39","published-print":{"date-parts":[[2026,9,29]]}},"alternative-id":["10.1073\/pnas.2613873123"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2613873123","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,23]]},"assertion":[{"value":"2026-04-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-18","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-23","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2613873123"}}