PUBLICATION
Bone Morphogenetic Protein signaling pathway - ethanol interactions disrupt palate formation independent of gata3
- Authors
- Lovely, C.B.
- ID
- ZDB-PUB-241127-8
- Date
- 2024
- Source
- Reproductive toxicology (Elmsford, N.Y.) 131: 108754 (Journal)
- Registered Authors
- Lovely, Ben
- Keywords
- Alcohol, Bone Morphogenetic Protein, Fetal Alcohol Spectrum Disorders, Genetics, Zebrafish, palate
- MeSH Terms
-
- Signal Transduction*/drug effects
- Mutation
- Animals
- GATA3 Transcription Factor*/genetics
- GATA3 Transcription Factor*/metabolism
- Palate*/abnormalities
- Palate*/drug effects
- Palate*/embryology
- Palate*/metabolism
- Zebrafish*
- Gene Expression Regulation, Developmental/drug effects
- Ethanol*/toxicity
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- Embryo, Nonmammalian/drug effects
- Bone Morphogenetic Proteins*/genetics
- Bone Morphogenetic Proteins*/metabolism
- PubMed
- 39586481 Full text @ Reprod. Toxicol.
Citation
Lovely, C.B. (2024) Bone Morphogenetic Protein signaling pathway - ethanol interactions disrupt palate formation independent of gata3. Reproductive toxicology (Elmsford, N.Y.). 131:108754.
Abstract
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 gata3 expression in the maxillary domain of the neural crest in the 1st pharyngeal arch, leading to palate defects while upregulation of human GATA3 rescues these defects. Here, we show that ethanol-treated Bmp mutants exhibit misshaped and/or broken trabeculae. Surprisingly, up regulation of GATA3 does not rescue ethanol-induced palate defects and gata3 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 10-18hours post-fertilization (hpf), prior to Bmp's regulation of gata3 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 gata3 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping