PUBLICATION
Mutations in the Bone Morphogenetic Protein signaling pathway sensitize zebrafish and humans to ethanol-induced jaw malformations
- Authors
- Klem, J.R., Schwantes-An, T.H., Abreu, M., Suttie, M., Gray, R., Vo, H., Conley, G., Foroud, T.M., Wetherill, L., CIFASD, Lovely, C.B.
- ID
- ZDB-PUB-250313-3
- Date
- 2025
- Source
- Disease models & mechanisms : (Journal)
- Registered Authors
- Lovely, Ben
- Keywords
- Alcohol, Endoderm, Fetal Alcohol Spectrum Disorders, Genetics, Jaw development, Zebrafish
- MeSH Terms
-
- Fetal Alcohol Spectrum Disorders/genetics
- Fetal Alcohol Spectrum Disorders/pathology
- Jaw Abnormalities*/chemically induced
- Jaw Abnormalities*/genetics
- Jaw Abnormalities*/pathology
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- Ethanol*/adverse effects
- Ethanol*/toxicity
- Gene Expression Regulation, Developmental/drug effects
- Bone Morphogenetic Proteins*/genetics
- Bone Morphogenetic Proteins*/metabolism
- Humans
- Animals
- Signal Transduction*/drug effects
- Signal Transduction*/genetics
- Morphogenesis/drug effects
- Endoderm/drug effects
- Endoderm/pathology
- Zebrafish*/embryology
- Zebrafish*/genetics
- Jaw*/pathology
- Mutation*/genetics
- PubMed
- 40067253 Full text @ Dis. Model. Mech.
Citation
Klem, J.R., Schwantes-An, T.H., Abreu, M., Suttie, M., Gray, R., Vo, H., Conley, G., Foroud, T.M., Wetherill, L., CIFASD, Lovely, C.B. (2025) Mutations in the Bone Morphogenetic Protein signaling pathway sensitize zebrafish and humans to ethanol-induced jaw malformations. Disease models & mechanisms. :.
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 BMPR1B associate with ethanol-related differences in jaw volume. Our results show that ethanol exposure disrupts proper morphogenesis of, and tissue interactions between, facial epithelia that mirror overall viscerocranial shape changes and are predictive for Bmp-ethanol associations in human jaw development. Our data provide a mechanistic paradigm linking ethanol to disrupted epithelial cell behaviors that underlie facial defects in FASD.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping