PUBLICATION

Sox7 controls arterial specification in conjunction with hey2 and efnb2 function

Authors
Hermkens, D.M., van Impel, A., Urasaki, A., Bussmann, J., Duckers, H.J., Schulte-Merker, S.
ID
ZDB-PUB-150403-2
Date
2015
Source
Development (Cambridge, England)   142(9): 1695-704 (Journal)
Registered Authors
Bussmann, Jeroen, Schulte-Merker, Stefan, van Impel, Andreas
Keywords
Vascular development, Arterial-venous specification, Sox7, Zebrafish
MeSH Terms
  • Animals
  • Animals, Genetically Modified/genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Morpholinos/genetics
  • DNA Primers/genetics
  • Arteries/embryology*
  • Morphogenesis/physiology*
  • Angiography
  • SOXF Transcription Factors/genetics*
  • SOXF Transcription Factors/metabolism
  • Regional Blood Flow/physiology
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism
  • In Situ Hybridization
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Vascular Endothelial Growth Factor Receptor-3/metabolism
  • Mutation/genetics
  • Basic Helix-Loop-Helix Transcription Factors/genetics
  • Gene Expression Regulation, Developmental/genetics
  • Gene Expression Regulation, Developmental/physiology*
(all 21)
PubMed
25834021 Full text @ Development
Abstract
SoxF family members have been linked to arterio-venous specification events and human pathological conditions, but in contrast to Sox17 and Sox18, a detailed in vivo analysis of a Sox7 mutant model is still lacking. In this study we generated zebrafish sox7 mutants to understand the role of Sox7 during vascular development. By in vivo imaging of transgenic zebrafish lines we show that sox7 mutants display a short circulatory loop around the heart as a result of aberrant connections between the lateral dorsal aorta (LDA) and either the venous primary head sinus (PHS) or the common cardinal vein (CCV). In situ hybridization and live observations in flt4:mCitrine transgenic embryos revealed increased expression levels of flt4 in arterial endothelial cells at the exact location of the aberrant vascular connections in sox7 mutants. An identical circulatory short loop could also be observed in newly generated mutants for hey2 and efnb2. By genetically modulating levels of sox7, hey2 and efnb2 we demonstrate a genetic interaction of sox7 with hey2 and efnb2. The specific spatially confined effect of loss of Sox7 function can be rescued by overexpressing the Notch intracellular domain (NICD) in arterial cells of sox7 mutants, placing Sox7 upstream of Notch in this aspect of arterial development. Hence, sox7 levels are crucial in arterial specification in conjunction with hey2 and efnb2 function, with mutants in all three genes displaying shunt formation and an arterial block.
Genes / Markers
Figures
Figure Gallery (6 images)
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
ha01TgTransgenic Insertion
    hu2971
      Point Mutation
      hu3393
        Point Mutation
        hu5626
          Point Mutation
          hu7135TgTransgenic Insertion
            hu10049TgTransgenic Insertion
              hu10320
                Insertion
                kca3TgTransgenic Insertion
                  s843TgTransgenic Insertion
                    s916TgTransgenic Insertion
                      1 - 10 of 12
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                      Human Disease / Model
                      No data available
                      Sequence Targeting Reagents
                      Target Reagent Reagent Type
                      hey2MO1-hey2MRPHLNO
                      hey2TALEN2-hey2TALEN
                      1 - 2 of 2
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                      Fish
                      Antibodies
                      No data available
                      Orthology
                      No data available
                      Engineered Foreign Genes
                      Marker Marker Type Name
                      CitrineEFGCitrine
                      DsRedEFGDsRed
                      EGFPEFGEGFP
                      GAL4FFEFGGAL4FF
                      mCherryEFGmCherry
                      1 - 5 of 5
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                      Mapping
                      No data available