{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T00:08:21Z","timestamp":1792627701206,"version":"4.5.0"},"reference-count":57,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T00:00:00Z","timestamp":1759449600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","award":["R00AA023560"],"award-info":[{"award-number":["R00AA023560"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","award":["R01AA031043"],"award-info":[{"award-number":["R01AA031043"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alcohol, Clinical and Experimental Research"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Fetal alcohol spectrum disorders (FASD) describe a spectrum of ethanol\u2010induced developmental defects. Ethanol susceptibility is modulated by genetics, but the underlying mechanisms remain poorly understood. In all vertebrates, complex cellular events give rise to the body plan, including gastrulation and morphogenesis of the endoderm and cranial neural crest (CNC\u2014gives rise to the facial skeleton). These events are crucial for establishing complex signaling interactions that drive embryo development, including the formation of the facial skeleton. In zebrafish, gastrulation occurs between 6 and 10\u2009h postfertilization (hpf), while endoderm\/CNC morphogenesis occurs between 10 and 24 hpf. In previous work, planar cell polarity (PCP) mutants are ethanol\u2010sensitive from 6 to 24 hpf (covering both gastrulation and endoderm\/CNC morphogenesis), exhibiting multiple defects in the forming head. This raises the question of whether ethanol during both these time windows drives PCP\u2010ethanol defects. We hypothesize that PCP mutants are ethanol\u2010sensitive from 10 to 24 hpf, after gastrulation. We also hypothesize that bone morphogenetic protein (BMP) signaling (ethanol\u2010sensitive 10\u201318 hpf) interacts with and sensitizes the PCP pathway to ethanol.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We treated PCP\/BMP mutants with ethanol over various time windows between 6 and 30 hpf and combined morphometric and linear measurements to examine facial development.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We show that PCP mutants are largely ethanol\u2010sensitive from 10 to 24 hpf. We also show that BMP mutants sensitize PCP mutants to ethanol and lead to novel ethanol\u2010independent midline craniofacial defects. Our results suggest that the ethanol\u2010sensitive role of the PCP pathway occurs after gastrulation, during endoderm\/CNC morphogenesis, and that the PCP and BMP pathways genetically interact during the morphogenetic events.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Ultimately, our work builds on a mechanistic paradigm of ethanol\u2010induced birth defects we have been developing, connecting the conceptual framework with concrete cellular events that could be ethanol\u2010sensitive beyond facial development.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/acer.70175","type":"journal-article","created":{"date-parts":[[2025,10,4]],"date-time":"2025-10-04T06:09:24Z","timestamp":1759558164000},"page":"2502-2519","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Interactions between the bone morphogenetic protein and the planar cell polarity pathways lead to distinctive ethanol\u2010induced facial defects"],"prefix":"10.1111","volume":"49","author":[{"given":"Ra\u00e8den","family":"Gray","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Genetics and Alcohol Research Center, School of Medicine University of Louisville  Louisville Kentucky USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Lloyd","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Genetics and Alcohol Research Center, School of Medicine University of Louisville  Louisville Kentucky USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7838-5823","authenticated-orcid":false,"given":"C. 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