PUBLICATION
Loss of the epithelial transcription factor grhl3 leads to variably penetrant developmental phenotypes in zebrafish
- Authors
- Mathiyalagan, N., Johnson, T.K., Di Pastena, Z., Fuller, J.N., Miles, L.B., Dworkin, S.
- ID
- ZDB-PUB-250221-4
- Date
- 2025
- Source
- Developmental Dynamics : an official publication of the American Association of Anatomists : (Journal)
- Registered Authors
- Dworkin, Seb, Miles, Lee
- Keywords
- Grainyhead‐like 3, gene–environment interaction, intestine, phenotypic penetrance, zebrafish
- MeSH Terms
-
- Transcription Factors*/genetics
- Transcription Factors*/metabolism
- Embryonic Development/genetics
- Animals
- Gene Expression Regulation, Developmental
- Phenotype
- Zebrafish*/embryology
- Zebrafish*/genetics
- DNA-Binding Proteins*/genetics
- DNA-Binding Proteins*/metabolism
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- Penetrance
- PubMed
- 39976312 Full text @ Dev. Dyn.
Citation
Mathiyalagan, N., Johnson, T.K., Di Pastena, Z., Fuller, J.N., Miles, L.B., Dworkin, S. (2025) Loss of the epithelial transcription factor grhl3 leads to variably penetrant developmental phenotypes in zebrafish. Developmental Dynamics : an official publication of the American Association of Anatomists. :.
Abstract
Background Environmental influence is critical for embryogenesis but is significantly under-appreciated under lab conditions, which are not typically designed to robustly test environmental variability. Here, we report environmental effects on the developmental phenotype of zebrafish lacking the transcription factor Grainyhead-like 3 (grhl3), a highly conserved gene that is pivotal in epithelial barrier formation, neurulation, craniofacial development, and convergence-extension.
Results We had previously reported that deletion of grhl3 led to embryonic lethality by 11 h post-fertilization (hpf); however, housing these grhl3-lines in a different aquatic facility led to substantial differences in phenotypic presentation in grhl3-nullizygous (grhl3-/-) embryos. We found that grhl3-/- embryos presented with three distinct phenotypes, characterized by significant reductions in body length, aberrant orofacial cavity formation and craniofacial morphogenesis and impaired intestinal barrier maintenance.
Conclusions Our study describes a new model of partial phenotypic penetrance in genetically identical embryos. This may serve as a valuable model system in which to understand gene-environment interactions in developmental and epithelial homeostasis.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping