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Most craniofacial disorders are associated with defects in a migratory stem and progenitor cell population, which is designated the neural crest (NC). Musculocontractural Ehlers\u2013Danlos syndrome (MCEDS) is a heritable connective tissue disorder with distinct craniofacial features; this syndrome comprises multiple congenital malformations that are caused by dysfunction of dermatan sulfate (DS) biosynthetic enzymes, including DS epimerase-1 (DS-epi1; also known as DSE). Studies in mice have extended our understanding of DS-epi1 in connective tissue maintenance; however, its role in fetal development is not understood. We demonstrate that DS-epi1 is important for the generation of isolated iduronic acid residues in chondroitin sulfate (CS)\/DS proteoglycans in early Xenopus embryos. The knockdown of DS-epi1 does not affect the formation of early NC progenitors; however, it impairs the correct activation of transcription factors involved in the epithelial\u2013mesenchymal transition (EMT) and reduces the extent of NC cell migration, which leads to a decrease in NC-derived craniofacial skeleton, melanocytes and dorsal fin structures. Transplantation experiments demonstrate a tissue-autonomous role for DS-epi1 in cranial NC cell migration in vivo. Cranial NC explant and single-cell cultures indicate a requirement of DS-epi1 in cell adhesion, spreading and extension of polarized cell processes on fibronectin. Thus, our work indicates a functional link between DS and NC cell migration. We conclude that NC defects in the EMT and cell migration might account for the craniofacial anomalies and other congenital malformations in MCEDS, which might facilitate the diagnosis and development of therapies for this distressing condition. Moreover, the presented correlations between human DS-epi1 expression and gene sets of mesenchymal character, invasion and metastasis in neuroblastoma and malignant melanoma suggest an association between DS and NC-derived cancers.<\/jats:p>","DOI":"10.1242\/dmm.024661","type":"journal-article","created":{"date-parts":[[2016,4,22]],"date-time":"2016-04-22T01:48:44Z","timestamp":1461289724000},"page":"607-620","source":"Crossref","is-referenced-by-count":31,"title":["Musculocontractural Ehlers\u2013Danlos syndrome and neurocristopathies: dermatan sulfate is required for <i>Xenopus<\/i> neural crest cells to migrate and adhere to fibronectin"],"prefix":"10.1242","volume":"9","author":[{"given":"Nad\u00e8ge","family":"Gouignard","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, Lund Stem Cell Center, Lund University 1 , Lund 221 84 , Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Maccarana","sequence":"additional","affiliation":[{"name":"Lund University 2 Department of Experimental Medical Science , , Lund 221 84 , Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ina","family":"Strate","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Lund Stem Cell Center, Lund University 1 , Lund 221 84 , Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristoffer","family":"von Stedingk","sequence":"additional","affiliation":[{"name":"Lund University 3 Department of Pediatrics , , Lund 223 63 , Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anders","family":"Malmstr\u00f6m","sequence":"additional","affiliation":[{"name":"Lund University 2 Department of Experimental Medical Science , , Lund 221 84 , Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0625-0006","authenticated-orcid":false,"given":"Edgar M.","family":"Pera","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Lund Stem Cell Center, Lund University 1 , Lund 221 84 , Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2024061302552077900_DMM024661C1","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1016\/S0012-1606(03)00277-X","article-title":"Integrin \u03b15\u03b21 supports the migration of Xenopus cranial neural crest on fibronectin","volume":"260","author":"Alfandari","year":"2003","journal-title":"Dev. 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