{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T06:50:27Z","timestamp":1777704627848,"version":"3.51.4"},"posted":{"date-parts":[[2024,6,11]]},"group-title":"Developmental Biology","reference-count":52,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,6,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  <jats:italic>IRF6<\/jats:italic>\n                  is a key genetic determinant of syndromic and non-syndromic cleft lip and palate. The ability to interrogate post-embryonic requirements of\n                  <jats:italic>Irf6<\/jats:italic>\n                  has been hindered, as global\n                  <jats:italic>Irf6<\/jats:italic>\n                  ablation in the mouse causes neonatal lethality. Prior work analyzing\n                  <jats:italic>Irf6<\/jats:italic>\n                  in mouse models defined its role in the embryonic surface epithelium and periderm where it is required to regulate cell proliferation and differentiation. Several reports have also described\n                  <jats:italic>Irf6<\/jats:italic>\n                  gene expression in other cell types, such as muscle, and neuroectoderm. However, analysis of a functional role in non-epithelial cell lineages has been incomplete due to the severity and lethality of the\n                  <jats:italic>Irf6<\/jats:italic>\n                  knockout model and the paucity of work with a conditional\n                  <jats:italic>Irf6<\/jats:italic>\n                  allele. Here we describe the generation and characterization of a new\n                  <jats:italic>Irf6<\/jats:italic>\n                  floxed mouse model and analysis of\n                  <jats:italic>Irf6<\/jats:italic>\n                  ablation in periderm and neural crest lineages. This work found that loss of\n                  <jats:italic>Irf6<\/jats:italic>\n                  in periderm recapitulates a mild\n                  <jats:italic>Irf6<\/jats:italic>\n                  null phenotype, suggesting that\n                  <jats:italic>Irf6<\/jats:italic>\n                  -mediated signaling in periderm plays a crucial role in regulating embryonic development. Further, conditional ablation of\n                  <jats:italic>Irf6<\/jats:italic>\n                  in neural crest cells resulted in an anterior neural tube defect of variable penetrance. The generation of this conditional\n                  <jats:italic>Irf6<\/jats:italic>\n                  allele allows for new insights into craniofacial development and new exploration into the post-natal role of\n                  <jats:italic>Irf6<\/jats:italic>\n                  .\n                <\/jats:p>","DOI":"10.1101\/2024.06.11.598425","type":"posted-content","created":{"date-parts":[[2024,6,11]],"date-time":"2024-06-11T14:16:30Z","timestamp":1718115390000},"source":"Crossref","is-referenced-by-count":5,"title":["Neural crest and periderm-specific requirements of\n                  <i>Irf6<\/i>\n                  during neural tube and craniofacial development"],"prefix":"10.64898","author":[{"given":"Shannon H.","family":"Carroll","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sogand","family":"Schafer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eileen","family":"Dalessandro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thach-Vu","family":"Ho","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Chai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric C.","family":"Liao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2024061703050883000_2024.06.11.598425v1.1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.01866-07"},{"key":"2024061703050883000_2024.06.11.598425v1.2","doi-asserted-by":"crossref","unstructured":"Bertol, J.W. , Johnston, S. , Ahmed, R. , Xie, V.K. , Hubka, K.M. , Cruz, L. , Nitschke, L. , Stetsiv, M. , Goering, J.P. , Nistor, P. , et al. (2022). TWIST1 interacts with beta\/delta-catenins during neural tube development and regulates fate transition in cranial neural crest cells. Development 149.","DOI":"10.1242\/dev.200068"},{"key":"2024061703050883000_2024.06.11.598425v1.3","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2011.272"},{"key":"2024061703050883000_2024.06.11.598425v1.4","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1110931108"},{"key":"2024061703050883000_2024.06.11.598425v1.5","doi-asserted-by":"crossref","unstructured":"Carroll, S.H. , Macias Trevino, C. , Li, E.B. , Kawasaki, K. , Myers, N. , Hallett, S.A. , Alhazmi, N. , Cotney, J. , Carstens, R.P. , and Liao, E.C . (2020). An Irf6-Esrp1\/2 regulatory axis controls midface morphogenesis in vertebrates. Development 147.","DOI":"10.1242\/dev.194498"},{"key":"2024061703050883000_2024.06.11.598425v1.6","doi-asserted-by":"publisher","DOI":"10.1177\/0022034516656787"},{"key":"2024061703050883000_2024.06.11.598425v1.7","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2016.84"},{"key":"2024061703050883000_2024.06.11.598425v1.8","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2012.269"},{"key":"2024061703050883000_2024.06.11.598425v1.9","doi-asserted-by":"publisher","DOI":"10.1242\/dev.080473"},{"key":"2024061703050883000_2024.06.11.598425v1.10","doi-asserted-by":"crossref","first-page":"7129","DOI":"10.1038\/s41598-017-06310-z","article-title":"Intercellular Genetic Interaction Between Irf6 and Twist1 during Craniofacial Development","volume":"7","year":"2017","journal-title":"Scientific reports"},{"key":"2024061703050883000_2024.06.11.598425v1.11","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1002\/dvdy.22786","article-title":"MCS9.7 enhancer activity is highly, but not completely, associated with expression of Irf6 and p63","volume":"241","year":"2012","journal-title":"Developmental dynamics : an official publication of the American Association of Anatomists"},{"key":"2024061703050883000_2024.06.11.598425v1.12","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2011.08.005"},{"key":"2024061703050883000_2024.06.11.598425v1.13","doi-asserted-by":"crossref","unstructured":"Fischer, A.H. , Jacobson, K.A. , Rose, J. , and Zeller, R . 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The NOTCH-RIPK4-IRF6-ELOVL4 Axis Suppresses Squamous Cell Carcinoma. 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