PUBLICATION

Identification of in vivo Hox13-binding sites reveals an essential locus controlling zebrafish brachyury expression

Authors
Ye, Z., Braden, C.R., Wills, A., Kimelman, D.
ID
ZDB-PUB-210602-8
Date
2021
Source
Development (Cambridge, England)   148(11): (Journal)
Registered Authors
Kimelman, David
Keywords
Brachyury, Hox genes, Neuromesodermal progenitors, Wnt signaling
MeSH Terms
  • Trans-Activators/metabolism
  • Binding Sites
  • Zebrafish/embryology
  • Zebrafish/genetics*
  • Zebrafish/metabolism*
  • Animals
  • Body Patterning
  • Somites/metabolism
  • Wnt Signaling Pathway
  • Embryonic Development
  • T-Box Domain Proteins/genetics*
  • T-Box Domain Proteins/metabolism*
  • Fetal Proteins/genetics*
  • Fetal Proteins/metabolism*
  • Gene Expression Regulation, Developmental
  • Mesoderm/metabolism
  • Transcription Factors/metabolism
  • Embryo, Mammalian/metabolism
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism*
(all 20)
PubMed
34061173 Full text @ Development
Abstract
During early embryogenesis, the vertebrate embryo extends from anterior to posterior because of the progressive addition of cells from a posteriorly localized neuromesodermal progenitor (NMp) population. An autoregulatory loop between Wnt and Brachyury/Tbxt is required for NMps to retain mesodermal potential and, hence, normal axis development. We recently showed that Hox13 genes help to support body axis formation and to maintain the autoregulatory loop, although the direct Hox13 target genes were unknown. Here, using a new method for identifying in vivo transcription factor-binding sites, we identified more than 500 potential Hox13 target genes in zebrafish. Importantly, we found two highly conserved Hox13-binding elements far from the tbxta transcription start site that also contain a conserved Tcf7/Lef1 (Wnt response) site. We show that the proximal of the two elements is sufficient to confer somitogenesis-stage expression to a tbxta promoter that, on its own, only drives NMp expression during gastrulation. Importantly, elimination of this proximal element produces shortened embryos due to aberrant formation of the most posterior somites. Our study provides a potential direct connection between Hox13 and regulation of the Wnt/Brachyury loop.
Genes / Markers
Figures
Figure Gallery (8 images)
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Expression
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
w249TgTransgenic Insertion
    w250TgTransgenic Insertion
      w251TgTransgenic Insertion
        1 - 3 of 3
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        Human Disease / Model
        No data available
        Sequence Targeting Reagents
        Target Reagent Reagent Type
        hoxa13bCRISPR4-hoxa13bCRISPR
        hoxa13bCRISPR5-hoxa13bCRISPR
        1 - 2 of 2
        Show
        Fish
        No data available
        Antibodies
        No data available
        Orthology
        No data available
        Engineered Foreign Genes
        Marker Marker Type Name
        GFPEFGGFP
        mCherryEFGmCherry
        1 - 2 of 2
        Show
        Mapping
        No data available
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        Citation
        Ye, Z., Braden, C.R., Wills, A., Kimelman, D. (2021) Identification of in vivo Hox13-binding sites reveals an essential locus controlling zebrafish brachyury expression. Development (Cambridge, England). 148(11):.