{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T17:26:10Z","timestamp":1784395570894,"version":"3.55.0"},"reference-count":40,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2019,4,2]],"date-time":"2019-04-02T00:00:00Z","timestamp":1554163200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2014HM017"],"award-info":[{"award-number":["ZR2014HM017"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2016HM79"],"award-info":[{"award-number":["ZR2016HM79"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["anatomypubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Developmental Dynamics"],"published-print":{"date-parts":[[2019,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The DENND1A has been identified as a guanine nucleotide exchange factor for small GTPase Rab35, which functions in endocytic trafficking to mediate the recycling of selective cargos. Genetic alterations within the <jats:italic>DENND1A<\/jats:italic> gene have been implicated in human disease such as polycystic ovary syndrome (PCOS). However, the role of DENND1A in developmental and reproductive processes is largely unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Using <jats:italic>Dennd1a<\/jats:italic> gene knockout mice, we uncovered that homogeneous Dennd1a\u2212\/\u2212 mutants died around embryonic day (E) 14.5. The brain of Dennd1a\u2212\/\u2212 embryos exhibited defects, partially attributed to the dysregulation of cell division and survival in the telencephalon. The transcription of <jats:italic>Fgf8<\/jats:italic> mRNA was ectopically elevated in the dorsal midline of telencephalon, concomitant with a decrease of active \u03b2\u2010catenin and <jats:italic>Axin2<\/jats:italic> in the brain of Dennd1a\u2212\/\u2212 embryos. During liver morphogenesis, the ablation of Dennd1a impaired hepatic cell proliferation, the differentiation of hepatocyte, and hepatic hematopoiesis. In addition, loss of Dennd1a also affected the development of primordial germ cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We demonstrate that Dennd1a, a susceptibility gene for PCOS, is essential for embryogenesis, probably through the mediation of endocytic recycling of selective cargos that are involved in cell signaling crucial for the development of multiple embryonic organ systems.<\/jats:p><\/jats:sec>","DOI":"10.1002\/dvdy.28","type":"journal-article","created":{"date-parts":[[2019,3,18]],"date-time":"2019-03-18T21:44:12Z","timestamp":1552945452000},"page":"351-362","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["<i>Dennd1a<\/i>, a susceptibility gene for polycystic ovary syndrome, is essential for mouse embryogenesis"],"prefix":"10.1002","volume":"248","author":[{"given":"Jingjing","family":"Shi","sequence":"first","affiliation":[{"name":"Center for Reproductive Medicine Shandong University  Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, School of Medicine Shandong University  Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongzhi","family":"Cao","sequence":"additional","affiliation":[{"name":"Center for Reproductive Medicine Shandong University  Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4704-8274","authenticated-orcid":false,"given":"Jiang","family":"Fu","sequence":"additional","affiliation":[{"name":"Center for Reproductive Medicine Shandong University  Jinan Shandong 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