{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T22:44:54Z","timestamp":1777589094627,"version":"3.51.4"},"reference-count":36,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2018,2,22]],"date-time":"2018-02-22T00:00:00Z","timestamp":1519257600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R01GM068812"],"award-info":[{"award-number":["R01GM068812"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["R01DE020843"],"award-info":[{"award-number":["R01DE020843"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004543","name":"China Scholarship Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004543","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genesis"],"published-print":{"date-parts":[[2018,3]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>BMP signaling plays a critical role in craniofacial development. Augmentation of BMPR1A signaling through neural crest\u2010specific expression of constitutively active <jats:italic>Bmpr1a<\/jats:italic> (<jats:italic>caBmpr1a<\/jats:italic>) results in craniofacial deformities in mice. To investigate whether deletion of <jats:italic>Tak1<\/jats:italic> may rescue the craniofacial deformities caused by enhanced Smad\u2010dependent signaling through caBMPR1A, we generated embryos to activate transcription of <jats:italic>caBmpr1a<\/jats:italic> transgene and ablate <jats:italic>Tak1<\/jats:italic> in neural crest derivatives at the same time. We found that deformities of the double mutant mice showed more severe than those with each single mutation, including median facial cleft and cleft palate. We found higher levels of cell death in the medial nasal and the lateral nasal processes at E10.5 in association with higher levels of p53 in the double mutant embryos. We also found higher levels of pSmad1\/5\/9 in the lateral nasal processes at E10.5 in the double mutant embryos. Western analyses revealed that double mutant embryos showed similar degrees of upregulation of pSmad1\/5\/9 with <jats:italic>caBmpr1a<\/jats:italic> or <jats:italic>Tak1<\/jats:italic>\u2010cKO embryos while the double mutant embryos showed higher levels of phospho\u2010p38 than <jats:italic>caBmpr1a<\/jats:italic> or <jats:italic>Tak1\u2010<\/jats:italic>cKO embryos at E17.5, but not at E10.5. It suggested that deletion of <jats:italic>Tak1<\/jats:italic> aggravates the craniofacial deformities of the <jats:italic>caBmpr1a<\/jats:italic> mutants by increasing p53 and phospho\u2010p38 at different stage of embryogenesis.<\/jats:p>","DOI":"10.1002\/dvg.23093","type":"journal-article","created":{"date-parts":[[2018,2,22]],"date-time":"2018-02-22T09:18:40Z","timestamp":1519291120000},"source":"Crossref","is-referenced-by-count":11,"title":["Compound mutations in <i>Bmpr1a<\/i> and <i>Tak1<\/i> synergize facial deformities via increased cell death"],"prefix":"10.1002","volume":"56","author":[{"given":"Xia","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Biologic and Materials Sciences University of Michigan, School of Dentistry Ann Arbor Michigan"},{"name":"Department of Oral Pathology School and Hospital of Stomatology, Jilin University Changchun 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Radiation Biology and Medicine, Hiroshima University Hiroshima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Ninomiya\u2010Tsuji","sequence":"additional","affiliation":[{"name":"Department of Environmental and Molecular Toxicology North Carolina State University Raleigh North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongchen","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Oral Pathology School and Hospital of Stomatology, Jilin University Changchun China"},{"name":"Department of Oral Pathology, School of Stomatology China Medical University Shenyang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6268-4204","authenticated-orcid":false,"given":"Yuji","family":"Mishina","sequence":"additional","affiliation":[{"name":"Department of Biologic and Materials Sciences University of Michigan, School of Dentistry Ann Arbor 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