PUBLICATION
An evolutionarily conserved kernel of gata5, gata6, otx2 and prdm1a operates in the formation of endoderm in zebrafish
- Authors
- Tseng, W.F., Jang, T.H., Huang, C.B., and Yuh, C.H.
- ID
- ZDB-PUB-110719-20
- Date
- 2011
- Source
- Developmental Biology 357(2): 541-57 (Journal)
- Registered Authors
- Yuh, Chiou-Hwa (Cathy)
- Keywords
- kernel, mesendoderm, zebrafish
- MeSH Terms
-
- Base Sequence
- GATA5 Transcription Factor/genetics
- GATA5 Transcription Factor/metabolism
- DNA-Binding Proteins/genetics
- DNA-Binding Proteins/metabolism
- Molecular Sequence Data
- Gene Regulatory Networks/genetics*
- Endoderm/drug effects
- Endoderm/embryology*
- Endoderm/metabolism
- Reproducibility of Results
- Oligonucleotides, Antisense/pharmacology
- Gene Expression Regulation, Developmental/drug effects
- GATA Transcription Factors/genetics
- GATA Transcription Factors/metabolism
- Epistasis, Genetic/drug effects
- Genetic Loci/genetics
- Body Patterning/drug effects
- Body Patterning/genetics
- Zebrafish/embryology*
- Zebrafish/genetics*
- DNA Mutational Analysis
- Nuclear Proteins/genetics
- Nuclear Proteins/metabolism
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- Animals
- Evolution, Molecular*
- Gene Expression Profiling
- Protein Binding
- Otx Transcription Factors/genetics
- Otx Transcription Factors/metabolism
- Time Factors
- RNA, Messenger/genetics
- RNA, Messenger/metabolism
- Conserved Sequence/genetics*
- PubMed
- 21756893 Full text @ Dev. Biol.
Citation
Tseng, W.F., Jang, T.H., Huang, C.B., and Yuh, C.H. (2011) An evolutionarily conserved kernel of gata5, gata6, otx2 and prdm1a operates in the formation of endoderm in zebrafish. Developmental Biology. 357(2):541-57.
Abstract
An evolutionarily conserved subcircuit (kernel) dedicated to a specific developmental function is found at the top of the gene regulatory networks (GRNs) hierarchy. Here we comprehensively demonstrate that a pan-deuterostome endoderm specification kernel exists in zebrafish. We analyzed interactions among gata5, gata6, otx2 and prdm1a using specific morpholino knockdowns and measured the gene expression profiles by quantitative real-time RT-PCR and in situ hybridization. The mRNA rescue experiment validated the specificity of the morpholino knockdown. We found that the interactions among gata5, gata6, otx2 and prdm1a determine the initial specification of the zebrafish endoderm. Although otx2 can activate both gata5 and gata6, and the prdm1a/krox homologue also activates some endoderm transcription factors, a feedback loop from Gata to otx2 and prdm1a is missing. Furthermore, we found the positive regulation between gata5 and gata6 to further lock-on the mesendoderm specification by the Gata family. Chromatin immunoprecipitation was used to further validate the recruitment of Otx2 to the gata5 and gata6 loci. Functional assays revealed that module B of gata6 and the basal promoter of gata5 drive the gene at the mesendoderm, and mutational analysis demonstrated that Otx2 and Gata5/6 contribute to reporter gene activation. This is the first direct evidence for evolutionarily conserved endoderm specification across echinoderms and vertebrates.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping