{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T02:16:20Z","timestamp":1771035380039,"version":"3.50.1"},"reference-count":51,"publisher":"The Company of Biologists","issue":"15","license":[{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.biologists.com\/user-licence-1-2\/"}],"funder":[{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science, and Technology","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100007428","name":"Naito Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100007428","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100008732","name":"Uehara Memorial Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100008732","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100007449","name":"Takeda Science Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100007449","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,8,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>Grainyhead-like transcription factor 3 (GRHL3) directs surface ectoderm differentiation under the control of the canonical Wnt\/\u03b2-catenin pathway. However, the molecular mechanisms that control nuclear GRHL3 expression through \u03b2-catenin are not fully understood. Here, we show that the essential for mitotic growth 1 (EMG1) protein constitutes a protein complex with GRHL3, and that EMG1 is required for correct nuclear localization of GRHL3, and for activation of the canonical Wnt signaling pathway. Conditional knockout mutation of Emg1 in the GRHL3-positive surface ectoderm causes neural tube defects at the level of the spinal cord, i.e. spina bifida. Additionally, the severity of compound mutant phenotypes of Emg1 and Grhl3 indicates that they interact genetically in neurulation and palate development. These lines of evidence demonstrate that EMG1 cooperates with GRHL3 in \u03b2-catenin-mediated surface ectoderm differentiation. Since the EMG1 mutation causes Bowen\u2013Conradi syndrome and the GRHL3 mutation causes Van der Woude syndrome 2, both of which are associated with neural tube dysplasia and cleft palate, our study will help to improve our understanding of the pathogenic mechanisms of these two human genetic diseases.<\/jats:p>","DOI":"10.1242\/dev.204700","type":"journal-article","created":{"date-parts":[[2025,8,5]],"date-time":"2025-08-05T08:02:14Z","timestamp":1754380934000},"source":"Crossref","is-referenced-by-count":1,"title":["EMG1 cooperates with GRHL3 in \u03b2-catenin-mediated surface ectoderm differentiation to regulate neural tube closure"],"prefix":"10.1242","volume":"152","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1992-3473","authenticated-orcid":false,"given":"Chiharu","family":"Kimura-Yoshida","sequence":"first","affiliation":[{"name":"Research Institute, Osaka Women's and Children's Hospital, Osaka Prefectural Hospital Organization 1 Department of Molecular Embryology , , 840, Murodo-cho, Izumi, Osaka 594-1101 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyoko","family":"Mochida","sequence":"additional","affiliation":[{"name":"Research Institute, Osaka Women's and Children's Hospital, Osaka Prefectural Hospital Organization 1 Department of Molecular Embryology , , 840, Murodo-cho, Izumi, Osaka 594-1101 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chihiro","family":"Matsuno","sequence":"additional","affiliation":[{"name":"Research Institute, Osaka Women's and Children's Hospital, Osaka Prefectural Hospital Organization 1 Department of Molecular Embryology , , 840, Murodo-cho, Izumi, Osaka 594-1101 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keiko","family":"Kano","sequence":"additional","affiliation":[{"name":"Molecular Structure Center, Institute of Transformative Bio-Molecules (WPI-ITbM), Nagoya University 2 , Chikusa, Nagoya 464-8602 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emi","family":"Mishiro-Sato","sequence":"additional","affiliation":[{"name":"Molecular Structure Center, Institute of Transformative Bio-Molecules (WPI-ITbM), Nagoya University 2 , Chikusa, Nagoya 464-8602 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5916-6246","authenticated-orcid":false,"given":"Isao","family":"Matsuo","sequence":"additional","affiliation":[{"name":"Research Institute, Osaka Women's and Children's Hospital, Osaka Prefectural Hospital Organization 1 Department of Molecular Embryology , , 840, Murodo-cho, Izumi, Osaka 594-1101 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","published-online":{"date-parts":[[2025,8,5]]},"reference":[{"key":"2025080504020206800_DEV204700C1","doi-asserted-by":"publisher","first-page":"728","DOI":"10.1016\/j.ajhg.2009.04.017","article-title":"Mutation of a gene essential for ribosome biogenesis, EMG1, causes Bowen-Conradi syndrome","volume":"84","author":"Armistead","year":"2009","journal-title":"Am. 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