ArticlebioRxiv : the preprint server for biology2024
Mutations in the Bone Morphogenetic Protein signaling pathway sensitize zebrafish and humans to ethanol-induced jaw malformations.
Article in bioRxiv : the preprint server for biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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11 authors at 3 institutions in 2 countries.
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Abstract
Fetal Alcohol Spectrum Disorders (FASD) describe ethanol-induced developmental defects including craniofacial malformations. While ethanol-sensitive genetic mutations contribute to facial malformations, the impacted cellular mechanisms remain unknown. Bmp signaling is a key regulator of epithelial morphogenesis driving facial development, providing a possible ethanol-sensitive mechanism. We found that zebrafish mutants for Bmp signaling components are ethanol-sensitive and affect anterior pharyngeal endoderm shape and gene expression, indicating ethanol-induced malformations of the anterior pharyngeal endoderm cause facial malformations. Integrating FASD patient data, we provide the first evidence that variants in the human Bmp receptor gene Summary Statement: In this study, we apply a unique combination of zebrafish-based approaches and human genetic and facial dysmorphology analyses to resolve the cellular mechanisms driven by the ethanol-sensitive Bmp pathway.
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