PUBLICATION

Tmem88a mediates GATA-dependent specification of cardiomyocyte progenitors by restricting WNT signaling

Authors
Novikov, N., and Evans, T.
ID
ZDB-PUB-130816-37
Date
2013
Source
Development (Cambridge, England)   140(18): 3787-98 (Journal)
Registered Authors
Evans, Todd
Keywords
none
Datasets
GEO:GSE44026
MeSH Terms
  • Embryo, Nonmammalian/metabolism
  • Mesoderm/drug effects
  • Mesoderm/embryology
  • Mesoderm/metabolism
  • Mutation/genetics
  • Morpholinos/pharmacology
  • Myocardium/metabolism
  • Myocardium/pathology
  • Apoptosis/drug effects
  • Apoptosis/genetics
  • Down-Regulation/drug effects
  • Down-Regulation/genetics
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
  • GATA5 Transcription Factor/metabolism*
  • Wnt Signaling Pathway*/drug effects
  • Wnt Signaling Pathway*/genetics
  • Genetic Association Studies
  • Organogenesis/drug effects
  • Organogenesis/genetics
  • Membrane Proteins/genetics
  • Membrane Proteins/metabolism*
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Cell Lineage/drug effects
  • Cell Lineage/genetics
  • Cell Proliferation/drug effects
  • Stem Cells/cytology
  • Stem Cells/drug effects
  • Stem Cells/metabolism*
  • Animals
  • RNA Transport/genetics
  • Biomarkers/metabolism
  • Gene Expression Regulation, Developmental/drug effects
  • RNA, Messenger/genetics
  • RNA, Messenger/metabolism
  • Phenotype
  • Myocytes, Cardiac/cytology*
  • Myocytes, Cardiac/drug effects
  • Myocytes, Cardiac/metabolism
  • Body Patterning*/drug effects
  • Body Patterning*/genetics
  • GATA Transcription Factors/metabolism*
  • Cardiomyopathies/embryology
  • Cardiomyopathies/metabolism
  • Cardiomyopathies/pathology
(all 46)
PubMed
23903195 Full text @ Development
Abstract

Biphasic control of WNT signaling is essential during cardiogenesis, but how the pathway switches from promoting cardiac mesoderm to restricting cardiomyocyte progenitor fate is unknown. We identified genes expressed in lateral mesoderm that are dysregulated in zebrafish when both gata5 and gata6 are depleted, causing a block to cardiomyocyte specification. This screen identified tmem88a, which is expressed in the early cardiac progenitor field and was previously implicated in WNT modulation by overexpression studies. Depletion of tmem88a results in a profound cardiomyopathy, secondary to impaired cardiomyocyte specification. In tmem88a morphants, activation of the WNT pathway exacerbates the cardiomyocyte deficiency, whereas WNT inhibition rescues progenitor cells and cardiogenesis. We conclude that specification of cardiac fate downstream of gata5/6 involves activation of the tmem88a gene to constrain WNT signaling and expand the number of cardiac progenitors. Tmem88a is a novel component of the regulatory mechanism controlling the second phase of biphasic WNT activity essential for embryonic cardiogenesis.

Genes / Markers
Figures
Figure Gallery (18 images) / 2
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
f2TgTransgenic Insertion
    m39
      Deficiency
      twu34TgTransgenic Insertion
        w25TgTransgenic Insertion
          w26TgTransgenic Insertion
            w32TgTransgenic Insertion
              w34TgTransgenic Insertion
                zdf1
                  Point Mutation
                  1 - 8 of 8
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                  Human Disease / Model
                  No data available
                  Sequence Targeting Reagents
                  Target Reagent Reagent Type
                  gata5MO2-gata5MRPHLNO
                  gata6MO1-gata6MRPHLNO
                  tmem88aMO3-tmem88aMRPHLNO
                  tmem88aMO4-tmem88aMRPHLNO
                  1 - 4 of 4
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                  Fish
                  Antibodies
                  Orthology
                  No data available
                  Engineered Foreign Genes
                  Marker Marker Type Name
                  DsRed2EFGDsRed2
                  EGFPEFGEGFP
                  GFPEFGGFP
                  1 - 3 of 3
                  Show
                  Mapping
                  No data available