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Cranial neural crest cells (CNCCs) are unique to vertebrate embryos and emerge from the neural plate borders into multiple cell lineages that differentiate into bone, cartilage, neurons and glial cells. We have previously reported that Irf6 genetically interacts with Twist1 during CNCC-derived tissue formation. Here, we have investigated the mechanistic role of Twist1 and Irf6 at early stages of craniofacial development. Our data indicate that TWIST1 is expressed in endocytic vesicles at the apical surface and interacts with \u03b2\/\u03b4-catenins during neural tube closure, and Irf6 is involved in defining neural fold borders by restricting AP2\u03b1 expression. Twist1 suppresses Irf6 and other epithelial genes in CNCCs during the epithelial-to-mesenchymal transition (EMT) process and cell migration. Conversely, a loss of Twist1 leads to a sustained expression of epithelial and cell adhesion markers in migratory CNCCs. Disruption of TWIST1 phosphorylation in vivo leads to epidermal blebbing, edema, neural tube defects and CNCC-derived structural abnormalities. Altogether, this study describes a previously uncharacterized function of mammalian Twist1 and Irf6 in the neural tube and CNCCs, and provides new target genes for Twist1 that are involved in cytoskeletal remodeling.<\/jats:p>","DOI":"10.1242\/dev.200068","type":"journal-article","created":{"date-parts":[[2022,7,4]],"date-time":"2022-07-04T08:53:23Z","timestamp":1656924803000},"source":"Crossref","is-referenced-by-count":30,"title":["TWIST1 interacts with \u03b2\/\u03b4-catenins during neural tube development and regulates fate transition in cranial neural crest cells"],"prefix":"10.1242","volume":"149","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0898-1822","authenticated-orcid":false,"given":"Jessica W.","family":"Bertol","sequence":"first","affiliation":[{"name":"Center for Craniofacial Research 1 , Department of Diagnostic and Biomedical Sciences , , Houston, TX 77054 , USA"},{"name":"School of Dentistry, University of Texas Health Science Center at Houston 1 , Department of 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P.","family":"Goering","sequence":"additional","affiliation":[{"name":"The University of Kansas Medical Center 4 Department of Anatomy and Cell Biology , , Kansas City, KS 66160 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7826-5928","authenticated-orcid":false,"given":"Paul","family":"Nistor","sequence":"additional","affiliation":[{"name":"Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh 5 , Little France Drive, Edinburgh EH16 4UU , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4018-9480","authenticated-orcid":false,"given":"Sally","family":"Lowell","sequence":"additional","affiliation":[{"name":"Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh 5 , Little France Drive, Edinburgh EH16 4UU , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanne","family":"Hoskens","sequence":"additional","affiliation":[{"name":"ESAT\/PSI, KU Leuven 6 Department of Electrical Engineering , , Leuven 3001, Belgium"},{"name":"Medical Imaging Research Center, UZ Leuven 7 , Leuven 3000, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9489-9819","authenticated-orcid":false,"given":"Peter","family":"Claes","sequence":"additional","affiliation":[{"name":"ESAT\/PSI, KU Leuven 6 Department of Electrical Engineering , , Leuven 3001, Belgium"},{"name":"Medical Imaging Research Center, UZ Leuven 7 , Leuven 3000, Belgium"},{"name":"KU Leuven 8 Department of Human Genetics , , Leuven 3000, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seth M.","family":"Weinberg","sequence":"additional","affiliation":[{"name":"Center for Craniofacial and Dental Genetics 9 , Department of Oral and Craniofacial Sciences , , Pittsburgh, PA 15219"},{"name":"University of Pittsburgh 9 , Department of Oral and Craniofacial Sciences , , Pittsburgh, PA 15219"},{"name":"University of Pittsburgh 10 Department of Human Genetics , , Pittsburgh, PA 15260 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irfan","family":"Saadi","sequence":"additional","affiliation":[{"name":"The University of Kansas Medical Center 4 Department of Anatomy and Cell Biology , , Kansas City, KS 66160 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary C.","family":"Farach-Carson","sequence":"additional","affiliation":[{"name":"Center for Craniofacial Research 1 , Department of Diagnostic and Biomedical Sciences , , Houston, TX 77054 , USA"},{"name":"School of Dentistry, University of Texas Health Science Center at Houston 1 , Department of Diagnostic and Biomedical Sciences , , Houston, TX 77054 , USA"},{"name":"Rice University 2 Department of Bioengineering , , Houston, TX 77005 , 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