PUBLICATION

Specificity, redundancy and dosage thresholds among gata4/5/6 genes during zebrafish cardiogenesis

Authors
Sam, J., Mercer, E.J., Torregroza, I., Banks, K.M., Evans, T.
ID
ZDB-PUB-200626-2
Date
2020
Source
Biology Open   9(6): (Journal)
Registered Authors
Evans, Todd
Keywords
Embryogenesis, Heart development, Morphogenesis, Progenitor cells, Transcriptional regulation
MeSH Terms
  • GATA4 Transcription Factor/genetics*
  • GATA4 Transcription Factor/metabolism
  • Gene Targeting
  • Mutation
  • Gene Dosage
  • Animals
  • Organogenesis/genetics*
  • Phenotype
  • Genotype
  • Heart/embryology*
  • Gene Expression Regulation, Developmental*
  • GATA6 Transcription Factor/genetics*
  • GATA6 Transcription Factor/metabolism
  • Morphogenesis/genetics
  • GATA5 Transcription Factor/genetics*
  • GATA5 Transcription Factor/metabolism
  • Alleles
  • Zebrafish/embryology*
(all 18)
PubMed
32580940 Full text @ Biol. Open
Abstract
The Gata4/5/6 sub-family of zinc finger transcription factors regulate many aspects of cardiogenesis. However, critical roles in extra-embryonic endoderm also challenge comprehensive analysis during early mouse cardiogenesis, while zebrafish models have previously relied on knockdown assays. We generated targeted deletions to disrupt each gata4/5/6 gene in zebrafish and analyzed cardiac phenotypes in single, double and triple mutants. The analysis confirmed that loss of gata5 causes cardia bifida and validated functional redundancies for gata5/6 in cardiac precursor specification. Surprisingly, we discovered that gata4 is dispensable for early zebrafish development, while loss of one gata4 allele can suppress the bifid phenotype of the gata5 mutant. The gata4 mutants eventually develop an age-dependent cardiomyopathy. By combining combinations of mutant alleles, we show that cardiac specification depends primarily on an overall dosage of gata4/5/6 alleles rather than a specific gene. We also identify a specific role for gata6 in controlling ventricle morphogenesis through regulation of both the first and second heart field, while loss of both gata4/6 eliminates the ventricle. Thus, different developmental programs are dependent on total dosage, certain pairs, or specific gata4/5/6 genes during embryonic cardiogenesis.This article has an associated First Person interview with the first author of the paper.
Genes / Markers
Figures
Figure Gallery (11 images) / 2
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
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Citation
Sam, J., Mercer, E.J., Torregroza, I., Banks, K.M., Evans, T. (2020) Specificity, redundancy and dosage thresholds among gata4/5/6 genes during zebrafish cardiogenesis. Biology Open. 9(6):.