Asymmetric pitx2 expression in medaka epithalamus is regulated by nodal signaling through an intronic enhancer
Language English Country Germany Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
Grant support
14-20839P
Grantová Agentura České Republiky (CZ) - International
RVO68378050
Institute of Molecular Genetics of the Czech Academy of Sciences - International
LO1419
Ministerstvo Školství, Mládeže a Tělovýchovy (CZ) - International
PubMed
29663064
DOI
10.1007/s00427-018-0611-1
PII: 10.1007/s00427-018-0611-1
Knihovny.cz E-resources
- Keywords
- Asymmetry, Enhancer, Epithalamus, Medaka, Transgene, pitx2,
- MeSH
- Embryo, Nonmammalian cytology metabolism MeSH
- Epithalamus embryology metabolism MeSH
- Forkhead Transcription Factors genetics metabolism MeSH
- Functional Laterality MeSH
- Homeobox Protein PITX2 MeSH
- Homeodomain Proteins genetics metabolism MeSH
- Introns * MeSH
- Mesoderm embryology metabolism MeSH
- Oryzias embryology genetics MeSH
- Nodal Protein genetics metabolism MeSH
- Signal Transduction MeSH
- Transgenes genetics MeSH
- Transcription Factors genetics metabolism MeSH
- Binding Sites MeSH
- Gene Expression Regulation, Developmental * MeSH
- Green Fluorescent Proteins genetics metabolism MeSH
- Enhancer Elements, Genetic * MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- enhanced green fluorescent protein MeSH Browser
- Forkhead Transcription Factors MeSH
- Homeodomain Proteins MeSH
- Nodal Protein MeSH
- Transcription Factors MeSH
- Green Fluorescent Proteins MeSH
The epithalamic region of fishes shows prominent left-right asymmetries that are executed by nodal signaling upstream of the asymmetry-determining transcription factor pitx2. Previous reports have identified that nodal controls the left-sided pitx2 expression in the lateral plate mesoderm through an enhancer present in the last intron of this gene. However, whether similar regulation occurs also in the case of epithalamic asymmetry is currently unresolved. Here, we address some of the cis-regulatory information that control asymmetric pitx2 expression in epithalamus by presenting a Tg(pitx2:EGFP) 116-17 transgenic medaka model, which expresses enhanced green fluorescent protein (EGFP) under control of an intronic enhancer. We show that this transgene recapitulates epithalamic expression of the endogenous pitx2 and that it responds to nodal signaling inhibition. Further, we identify that three foxh1-binding sites present in this enhancer modulate expression of the transgene and that the second site is absolutely necessary for the left-sided epithalamic expression while the other two sites may have subtler regulative roles. We provide evidence that left-sided epithalamic pitx2 expression is controlled through an enhancer present in the last intron of this gene and that the regulatory logic underlying asymmetric pitx2 expression is shared between epithalamic and lateral plate mesoderm regions.
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