PUBLICATION

ndrg4 is required for normal myocyte proliferation during early cardiac development in zebrafish

Authors
Qu, X., Jia, H., Garrity, D.M., Tompkins, K., Batts, L., Appel, B., Zhong, T.P., and Baldwin, H.S.
ID
ZDB-PUB-080415-16
Date
2008
Source
Developmental Biology   317(2): 486-496 (Journal)
Registered Authors
Garrity, Deborah, Zhong, Tao P.
Keywords
Zebrafish, ndrg4, Cardiogenesis, Myocardium, tbx5, tbx20
MeSH Terms
  • Heart/embryology
  • Phenotype*
  • Bone Morphogenetic Proteins/metabolism
  • Bone Morphogenetic Protein 4
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
  • Myocytes, Cardiac/metabolism
  • Myocytes, Cardiac/physiology*
  • Nerve Tissue Proteins/genetics
  • Nerve Tissue Proteins/metabolism*
  • Oligonucleotides/genetics
  • Mutation/genetics
  • Animals
  • Cell Proliferation
  • Zebrafish/embryology*
  • Versicans/metabolism
  • Muscle Proteins/genetics
  • Muscle Proteins/metabolism*
  • T-Box Domain Proteins/metabolism
  • Cloning, Molecular
  • In Situ Hybridization
(all 21)
PubMed
18407257 Full text @ Dev. Biol.
Abstract
NDRG4 is a novel member of the NDRG family (N-myc downstream-regulated gene). The roles of NDRG4 in development have not previously been evaluated. We show that, during zebrafish embryonic development, ndrg4 is expressed exclusively in the embryonic heart, the central nervous system (CNS) and the sensory system. Ndrg4 knockdown in zebrafish embryos causes a marked reduction in proliferative myocytes and results in hypoplastic hearts. This growth defect is associated with cardiac phenotypes in morphogenesis and function, including abnormal heart looping, inefficient circulation and weak contractility. We reveal that ndrg4 is required for restricting the expression of versican and bmp4 to the developing atrioventricular canal. This constellation of ndrg4 cardiac defects phenocopies those seen in mutant hearts of heartstrings (hst), the tbx5 loss-of-function mutants in zebrafish. We further show that ndrg4 expression is significantly decreased in hearts with reduced tbx5 activities. Conversely, increased expression of tbx5 that is due to tbx20 knockdown leads to an increase in ndrg4 expression. Together, our studies reveal an essential role of ndrg4 in regulating proliferation and growth of cardiomyocytes, suggesting that ndrg4 may function downstream of tbx5 during heart development and growth.
Genes / Markers
Figures
Figure Gallery (11 images) / 2
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
f1TgTransgenic Insertion
    f2TgTransgenic Insertion
      m21
        Point Mutation
        1 - 3 of 3
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        Human Disease / Model
        No data available
        Sequence Targeting Reagents
        Target Reagent Reagent Type
        ndrg4MO1-ndrg4MRPHLNO
        ndrg4MO2-ndrg4MRPHLNO
        tbx5aMO1-tbx5aMRPHLNO
        tbx20MO1-tbx20MRPHLNO
        1 - 4 of 4
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        Fish
        Antibodies
        No data available
        Orthology
        Gene Orthology
        ndrg4
        1 - 1 of 1
        Show
        Engineered Foreign Genes
        Marker Marker Type Name
        DsRed2EFGDsRed2
        GFPEFGGFP
        1 - 2 of 2
        Show
        Mapping
        No data available