{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T17:43:37Z","timestamp":1792691017777,"version":"4.5.0"},"reference-count":92,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2021,10,23]],"date-time":"2021-10-23T00:00:00Z","timestamp":1634947200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,4,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>CRK and CRKL encode cytoplasmic adaptors that contribute to the etiology of congenital heart disease. Neural crest cells (NCCs) are required for cardiac outflow tract (OFT) septation and aortic arch formation. The roles of Crk\/Crkl in NCCs during mouse cardiovascular development remain unknown. To test this, we inactivated Crk and\/or Crkl in NCCs. We found that the loss of Crk, rather than Crkl, in NCCs resulted in double outlet right ventricle, while loss of both Crk\/Crkl in NCCs resulted in severe defects with earlier lethality due to failed OFT septation and severe dilation of the pharyngeal arch arteries (PAAs). We found that these defects are due to altered cell morphology resulting in reduced localization of NCCs to the OFT and failed integrity of the PAAs, along with reduced expression of Integrin signaling genes. Further, molecular studies identified reduced differentiation of vascular smooth muscle cells that may in part be due to altered Notch signaling. Additionally, there is increased cellular stress that leads to modest increase in apoptosis. Overall, this explains the mechanism for the Crk\/Crkl phenotype.<\/jats:p>","DOI":"10.1093\/hmg\/ddab313","type":"journal-article","created":{"date-parts":[[2021,10,21]],"date-time":"2021-10-21T19:09:52Z","timestamp":1634843392000},"page":"1197-1215","source":"Crossref","is-referenced-by-count":8,"title":["<i>Crk<\/i> and <i>Crkl<\/i> have shared functions in neural crest cells for cardiac outflow tract septation and vascular smooth muscle differentiation"],"prefix":"10.1093","volume":"31","author":[{"given":"Lijie","family":"Shi","sequence":"first","affiliation":[{"name":"Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia E","family":"Racedo","sequence":"additional","affiliation":[{"name":"Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Diacou","sequence":"additional","affiliation":[{"name":"Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taeju","family":"Park","sequence":"additional","affiliation":[{"name":"Children's Mercy Research Institute, Children's Mercy Kansas City, Kansas City, MO 64108, USA"},{"name":"Department of Pediatrics, University of Missouri-Kansas City School of Medicine, Kansas City, MO 64108, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8076-4726","authenticated-orcid":false,"given":"Bernice E","family":"Morrow","sequence":"additional","affiliation":[{"name":"Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,10,23]]},"reference":[{"key":"2022042214143853000_ref1","doi-asserted-by":"crossref","first-page":"6348","DOI":"10.1038\/sj.onc.1204779","article-title":"Crk family adaptors-signalling complex formation and biological roles","volume":"20","author":"Feller","year":"2001","journal-title":"Oncogene"},{"key":"2022042214143853000_ref2","first-page":"4396","article-title":"A noncatalytic domain conserved among cytoplasmic protein-tyrosine kinases modifies the kinase function and transforming activity of Fujinami sarcoma virus P130gag-fps","volume":"6","author":"Sadowski","year":"1986","journal-title":"Mol. 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