{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T12:37:37Z","timestamp":1770727057395,"version":"3.49.0"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,6,15]],"date-time":"2021-06-15T00:00:00Z","timestamp":1623715200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011781","name":"Shriners Hospitals for Children","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011781","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>The primary cilium is a ubiquitous, microtubule-based cellular organelle. Primary cilia dysfunction results in a group of disorders termed ciliopathies. C2 domain containing 3 centriole elongation regulator (C2cd3), encodes a centriolar protein essential for ciliogenesis. Mutations in human C2CD3 are associated with the human ciliopathy Oral-Facial-Digital syndrome type 14 (OFD14). In order to better understand the etiology of ciliopathies including OFD14, we generated numerous murine models targeting C2cd3. Initial analysis revealed several tissue-specific isoforms of C2cd3, and while the loss of C2cd3 has previously been reported to result in exencephaly, tight mesencephalic flexure, pericardial edema, abnormal heart looping and a twisted body axis, further analysis revealed that genetic background may also contribute to phenotypic variation. Additional analyses of a conditional allelic series targeting C-terminal PKC-C2 domains or the N-terminal C2CD3N-C2 domain of C2cd3 revealed a variable degree of phenotypic severity, suggesting that while the N-terminal C2CD3N-C2 domain was critical for early embryonic development as a whole, there was also a craniofacial specific role for the C2CD3N-C2 domains. Together, through generation of novel models and evaluation of C2cd3 expression, these data provide valuable insight into mechanisms of pathology for craniofacial ciliopathies that can be further explored in the future.<\/jats:p>","DOI":"10.3389\/fcell.2021.647391","type":"journal-article","created":{"date-parts":[[2021,6,15]],"date-time":"2021-06-15T08:02:56Z","timestamp":1623744176000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Centriolar Protein C2cd3 Is Required for Craniofacial Development"],"prefix":"10.3389","volume":"9","author":[{"given":"Ching-Fang","family":"Chang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kari M.","family":"Brown","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanfen","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samantha A.","family":"Brugmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,6,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1038\/nature04370","article-title":"Dissection of epistasis in oligogenic Bardet-Biedl syndrome.","volume":"439","author":"Badano","year":"2006","journal-title":"Nature"},{"key":"B2","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1002\/ajmg.c.30231","article-title":"Making sense of cilia in disease: the human ciliopathies.","author":"Baker","year":"2009","journal-title":"Am. 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