{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T15:13:27Z","timestamp":1790522007254,"version":"4.1.0"},"reference-count":89,"publisher":"The Company of Biologists","license":[{"start":{"date-parts":[[2020,1,1]],"date-time":"2020-01-01T00:00:00Z","timestamp":1577836800000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/www.biologists.com\/user-licence-1-1\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01 GM114105"],"award-info":[{"award-number":["R01 GM114105"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Mutations in the RNA helicase DDX3 have emerged as a frequent cause of intellectual disability in humans. Because many patients carrying DDX3 mutations have additional defects in craniofacial structures and other tissues containing neural crest (NC)-derived cells, we hypothesized that DDX3 is also important for NC development. Using Xenopus tropicalis as a model, we show that DDX3 is required for normal NC induction and craniofacial morphogenesis by regulating AKT kinase activity. Depletion of DDX3 decreases AKT activity and AKT-dependent inhibitory phosphorylation of GSK3\u03b2, leading to reduced levels of \u03b2-catenin and Snai1, two GSK3\u03b2 substrates that are critical for NC induction. DDX3 function in regulating these downstream signaling events during NC induction is likely mediated by RAC1, a small GTPase whose translation depends on the RNA helicase activity of DDX3. These results suggest an evolutionarily conserved role of DDX3 in NC development by promoting AKT activity, and provide a potential mechanism for the NC-related birth defects displayed by patients harboring mutations in DDX3 and its downstream effectors in this signaling cascade.<\/jats:p>","DOI":"10.1242\/dev.184341","type":"journal-article","created":{"date-parts":[[2020,12,16]],"date-time":"2020-12-16T17:08:42Z","timestamp":1608138522000},"source":"Crossref","is-referenced-by-count":11,"title":["The RNA helicase DDX3 induces neural crest by promoting AKT activity"],"prefix":"10.1242","author":[{"given":"Mark","family":"Perfetto","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, University of Delaware, Newark, DE 19716, USA"},{"name":"Department of Biology, West Virginia University, Morgantown, WV 26506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolu","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Delaware, Newark, DE 19716, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Congyu","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Delaware, Newark, DE 19716, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Delaware, Newark, DE 19716, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natasha","family":"Yousaf","sequence":"additional","affiliation":[{"name":"Department of Biology, West Virginia University, Morgantown, WV 26506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiejing","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biology, West Virginia University, Morgantown, WV 26506, USA"},{"name":"Department of Clinical Laboratory, The Affiliated Hospital of KMUST, Medical School, Kunming University of Science and Technology, Kunming 650032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvette Y.","family":"Yien","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Delaware, Newark, DE 19716, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuo","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Delaware, Newark, DE 19716, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2020,1,1]]},"reference":[{"key":"2021042623000292500_DEV184341C1","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1016\/j.jmoldx.2017.04.001","article-title":"Overgrowth syndromes caused by somatic variants in the phosphatidylinositol 3-kinase\/AKT\/mammalian target of rapamycin pathway","volume":"19","author":"Akgumus","year":"2017","journal-title":"J. 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