PUBLICATION

Nppa and Nppb act redundantly during zebrafish cardiac development to confine AVC marker expression and reduce cardiac jelly volume

Authors
Grassini, D.R., Lagendijk, A.K., De Angelis, J.E., Da Silva, J., Jeanes, A., Zettler, N., Bower, N.I., Hogan, B.M., Smith, K.A.
ID
ZDB-PUB-180513-7
Date
2018
Source
Development (Cambridge, England)   145(12): (Journal)
Registered Authors
Da Silva, Jason, De Angelis, Jessica, Grassini, Daniela, Hogan, Ben M., Jeanes, Angela, Smith, Kelly
Keywords
ANF, Cardiac development, Cardiac jelly, Nppa, Zebrafish
MeSH Terms
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
  • Animals, Genetically Modified
  • Bone Morphogenetic Protein 4/genetics
  • Bone Morphogenetic Protein 4/metabolism
  • Natriuretic Peptide, Brain/genetics*
  • Animals
  • Receptors, Atrial Natriuretic Factor/genetics*
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • T-Box Domain Proteins/metabolism
  • Heart/embryology*
  • Versicans/metabolism
  • Hyaluronan Synthases/metabolism
  • Atrial Natriuretic Factor/genetics*
  • Heart Defects, Congenital/genetics
  • Gene Editing
(all 17)
PubMed
29752386 Full text @ Development
Abstract
Atrial natriuretic peptide (nppa/anf) and brain natriuretic peptide (nppb/bnp) form a gene cluster with expression in the chambers of the developing heart. Despite restricted expression, a function in cardiac development has not been demonstrated by mutant analysis. This is attributed to functional redundancy; however, their genomic location in cis has impeded formal analysis. Using genome editing, we have generated mutants for nppa and nppb, and found that single mutants were indistinguishable from wild type, whereas nppa/nppb double mutants displayed heart morphogenesis defects and pericardial oedema. Analysis of atrioventricular canal (AVC) markers show expansion of bmp4, tbx2b, has2 and versican expression into the atrium of double mutants. This expanded expression correlates with increased extracellular matrix in the atrium. Using a biosensor for hyaluronic acid to measure the cardiac jelly (cardiac extracellular matrix), we confirmed cardiac jelly expansion in nppa/nppb double mutants. Finally, bmp4 knockdown rescued the expansion of has2 expression and cardiac jelly in double mutants. This definitively shows that nppa and nppb function redundantly during cardiac development to restrict gene expression to the AVC, preventing excessive cardiac jelly synthesis in the atrial chamber.
Genes / Markers
Figures
Figure Gallery (8 images)
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
f2TgTransgenic Insertion
    s916TgTransgenic Insertion
      uq7ksTgTransgenic Insertion
        uq19ks
          Small Deletion
          uq20ks
            Insertion
            uq21ks
              Insertion
              uq25bhTgTransgenic Insertion
                y7TgTransgenic Insertion
                  1 - 8 of 8
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                  Human Disease / Model
                  No data available
                  Sequence Targeting Reagents
                  Target Reagent Reagent Type
                  bmp4MO1-bmp4MRPHLNO
                  bmp4MO3-bmp4MRPHLNO
                  nppaTALEN1-nppaTALEN
                  nppbCRISPR1-nppbCRISPR
                  tp53MO4-tp53MRPHLNO
                  1 - 5 of 5
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                  Fish
                  Antibodies
                  Orthology
                  No data available
                  Engineered Foreign Genes
                  Marker Marker Type Name
                  DsRed2EFGDsRed2
                  EGFPEFGEGFP
                  mCherryEFGmCherry
                  1 - 3 of 3
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                  Mapping
                  No data available