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GRHL2 activates expression of several epithelial genes, however additional molecular targets and functional processes regulated by GRHL2 in the NNE remain to be determined, as well as the underlying cause of the NTDs in Grhl2 mutants. Here, we find that Grhl2 loss results in abnormal mesenchymal phenotypes in the NNE, including aberrant Vimentin expression and increased cellular dynamics that affects the NNE and neural crest cells. The resulting loss of NNE integrity contributes to an inability of the cranial neural folds to move toward the midline and results in NTD. Further, we identified Esrp1, Sostdc1, Fermt1, Tmprss2 and Lamc2, novel NNE-expressed genes that are downregulated in Grhl2 mutants. Our in vitro assays show they act as suppressors of the epithelial-to-mesenchymal transition (EMT). Thus, GRHL2 promotes the epithelial nature of the NNE during the dynamic events of neural tube formation by both activating key epithelial genes and actively suppressing EMT through novel downstream EMT suppressors.<\/jats:p>","DOI":"10.1242\/dev.129825","type":"journal-article","created":{"date-parts":[[2016,2,23]],"date-time":"2016-02-23T03:24:13Z","timestamp":1456197853000},"source":"Crossref","is-referenced-by-count":40,"title":["Grainyhead-like 2 downstream targets act to suppress EMT during neural tube closure"],"prefix":"10.1242","author":[{"given":"Heather J.","family":"Ray","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Cell Biology Stem Cells and Development Graduate Program, University of Colorado Anschutz Medical Campus and Children's Hospital Colorado, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lee A.","family":"Niswander","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Cell Biology Stem Cells and Development Graduate Program, University of Colorado Anschutz Medical Campus and Children's Hospital Colorado, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2021042608480511700_DEV129825C1","doi-asserted-by":"publisher","first-page":"4875","DOI":"10.1158\/0008-5472.CAN-13-3579","article-title":"TRIM29 suppresses TWIST1 and invasive breast cancer behavior","volume":"74","author":"Ai","year":"2014","journal-title":"Cancer Res."},{"key":"2021042608480511700_DEV129825C2","doi-asserted-by":"publisher","first-page":"2704","DOI":"10.1681\/asn.2014080759","article-title":"A Grainyhead-Like 2\/Ovo-Like 2 pathway regulates renal epithelial barrier function and lumen expansion","volume":"26","author":"Aue","year":"2015","journal-title":"J. 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