{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,8]],"date-time":"2026-11-08T11:40:07Z","timestamp":1794138007407,"version":"4.8.0"},"reference-count":68,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2006,6,7]],"date-time":"2006-06-07T00:00:00Z","timestamp":1149638400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0"},{"start":{"date-parts":[[2006,6,7]],"date-time":"2006-06-07T00:00:00Z","timestamp":1149638400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Dev Biol"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Craniofacial birth defects result from defects in cranial neural crest (NC) patterning and morphogenesis. The vertebrate craniofacial skeleton is derived from cranial NC cells and the patterning of these cells occurs within the pharyngeal arches. Substantial efforts have led to the identification of several genes required for craniofacial skeletal development such as the <jats:italic>endothelin-1 (edn1)<\/jats:italic> signaling pathway that is required for lower jaw formation. However, many essential genes required for craniofacial development remain to be identified.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Through screening a collection of insertional zebrafish mutants containing approximately 25% of the genes essential for embryonic development, we present the identification of 15 essential genes that are required for craniofacial development. We identified 3 genes required for hyomandibular development. We also identified zebrafish models for Campomelic Dysplasia and Ehlers-Danlos syndrome. To further demonstrate the utility of this method, we include a characterization of the <jats:italic>wdr68<\/jats:italic> gene. We show that <jats:italic>wdr68<\/jats:italic> acts upstream of the <jats:italic>edn1<\/jats:italic> pathway and is also required for formation of the upper jaw equivalent, the palatoquadrate. We also present evidence that the level of <jats:italic>wdr68<\/jats:italic> activity required for <jats:italic>edn1<\/jats:italic> pathway function differs between the 1<jats:sup>st<\/jats:sup> and 2<jats:sup>nd<\/jats:sup> arches. Wdr68 interacts with two minibrain-related kinases, Dyrk1a and Dyrk1b, required for embryonic growth and myotube differentiation, respectively. We show that a GFP-Wdr68 fusion protein localizes to the nucleus with Dyrk1a in contrast to an engineered loss of function mutation Wdr68-T284F that no longer accumulated in the cell nucleus and failed to rescue <jats:italic>wdr68<\/jats:italic> mutant animals. Wdr68 homologs appear to exist in all eukaryotic genomes. Notably, we found that the Drosophila <jats:italic>wdr68<\/jats:italic> homolog <jats:italic>CG14614<\/jats:italic> could substitute for the vertebrate <jats:italic>wdr68<\/jats:italic> gene even though insects lack the NC cell lineage.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>This work represents a systematic identification of approximately 25% of the essential genes required for craniofacial development. The identification of zebrafish models for two human disease syndromes indicates that homologs to the other genes are likely to also be relevant for human craniofacial development. The initial characterization of <jats:italic>wdr68<\/jats:italic> suggests an important role in craniofacial development for the highly conserved Wdr68-Dyrk1 protein complexes.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/1471-213x-6-28","type":"journal-article","created":{"date-parts":[[2006,6,7]],"date-time":"2006-06-07T18:29:50Z","timestamp":1149704990000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":85,"title":["A zebrafish screen for craniofacial mutants identifies wdr68 as a highly conserved gene required for endothelin-1 expression"],"prefix":"10.1186","volume":"6","author":[{"given":"Robert M","family":"Nissen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Amsterdam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy","family":"Hopkins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2006,6,7]]},"reference":[{"key":"107_CR1","first-page":"698","volume-title":"Vertebrate Paleontology and Evolution","author":"RL Carroll","year":"1988","unstructured":"Carroll RL: Vertebrate Paleontology and Evolution. 1988, W. 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