{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T23:36:17Z","timestamp":1768520177765,"version":"3.49.0"},"posted":{"date-parts":[[2024,11,15]]},"group-title":"Developmental Biology","reference-count":82,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,11,15]],"date-time":"2024-11-15T00:00:00Z","timestamp":1731628800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,11,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Fetal Alcohol Spectrum Disorders (FASD) describes a wide array of neurological defects and craniofacial malformations, associated with ethanol teratogenicity. While there is growing evidence for a genetic component to FASD, little is known of the genes underlying these ethanol-induced defects. Along with timing and dosage, genetic predispositions may help explain the variability within FASD. From a screen for gene-ethanol interactions, we found that mutants for Bmp signaling components are ethanol-sensitive leading to defects in the zebrafish palate. Loss of Bmp signaling results in reductions in\n                  <jats:italic>gata3<\/jats:italic>\n                  expression in the maxillary domain of the neural crest in the 1st pharyngeal arch, leading to palate defects while upregulation of human\n                  <jats:italic>GATA3<\/jats:italic>\n                  rescues these defects. Here, we show that ethanol-treated Bmp mutants exhibit misshaped and\/or broken trabeculae. Surprisingly, up regulation of\n                  <jats:italic>GATA3<\/jats:italic>\n                  does not rescue ethanol-induced palate defects and\n                  <jats:italic>gata3<\/jats:italic>\n                  expression was not altered in ethanol-treated Bmp mutants or dorsomorphin-treated larvae. Timing of ethanol sensitivity shows that Bmp mutants are ethanol sensitive from 10-18 hours post-fertilization (hpf), prior to Bmp\u2019s regulation of\n                  <jats:italic>gata3<\/jats:italic>\n                  in palate formation. This is consistent with our previous work with dorsomorphin-dependent knock down of Bmp signaling from 10-18 hpf disrupting endoderm formation and subsequent jaw development. Overall, this suggests that ethanol disrupts Bmp-dependent palate development independent of and earlier than the role of\n                  <jats:italic>gata3<\/jats:italic>\n                  in palate formation by disrupting epithelial development. Ultimately, these data demonstrate that zebrafish is a useful model to identify and characterize gene-ethanol interactions and this work will directly inform our understanding of FASD.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Highlights<\/jats:title>\n                  <jats:list list-type=\"bullet\">\n                    <jats:list-item>\n                      <jats:p>Bmp pathway mutants are ethanol sensitive resulting in palate defects.<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>\n                        Ethanol disrupts Bmp-dependent palate development independent of\n                        <jats:italic>gata3<\/jats:italic>\n                        .\n                      <\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Timing of ethanol sensitivity suggests ethanol disrupts Bmp-dependent epithelial morphogenesis.<\/jats:p>\n                    <\/jats:list-item>\n                  <\/jats:list>\n                <\/jats:sec>","DOI":"10.1101\/2024.11.15.623833","type":"posted-content","created":{"date-parts":[[2024,11,15]],"date-time":"2024-11-15T17:55:19Z","timestamp":1731693319000},"source":"Crossref","is-referenced-by-count":0,"title":["Bone Morphogenetic Protein signaling pathway \u2013 ethanol interactions disrupt palate formation independent of\n                  <i>gata3<\/i>"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7838-5823","authenticated-orcid":false,"given":"C. 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