PUBLICATION

Tcf7l1 proteins cell autonomously restrict cardiomyocyte and promote endothelial specification in zebrafish

Authors
Sorrell, M.R., Dohn, T.E., D'Aniello, E., and Waxman, J.S.
ID
ZDB-PUB-130703-37
Date
2013
Source
Developmental Biology   380(2): 199-210 (Journal)
Registered Authors
Waxman, Joshua
Keywords
wnt signaling, Tcf7l1, cardiomyocyte development, endothelial cell development, zebrafish
MeSH Terms
  • Animals
  • Cell Differentiation
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/physiology*
  • Myocytes, Cardiac/cytology*
  • Zebrafish/embryology*
  • Transcription Factor 7-Like 1 Protein/genetics
  • Transcription Factor 7-Like 1 Protein/physiology*
  • Body Patterning
  • Endothelial Cells/cytology*
  • Transcription, Genetic
  • Wnt Signaling Pathway
(all 12)
PubMed
23707897 Full text @ Dev. Biol.
Abstract

Tcf7l1 (formerly Tcf3) proteins are conserved transcription factors whose function as transcriptional repressors is relieved through interactions with β-catenin. Although the functions of Tcf7l1 proteins have been studied in many developmental contexts, whether this conserved mediator of Wnt signaling is required for appropriate cardiomyocyte (CM) development has not been investigated. We find that Tcf7l1 proteins are necessary during two developmental periods to limit CM number in zebrafish embryos: prior to gastrulation and after the initial wave of CM differentiation. In contrast to partially redundant roles in anterior neural patterning, we find that Tcf7l1a and Tcf7l1b have non-redundant functions with respect to restricting CM specification during anterior mesodermal patterning, suggesting that between the two zebrafish Tcf7l1 paralogs there is a limit to the transcriptional repression provided during early CM specification. Using cell transplantation experiments, we determine that the Tcf7l1 paralogs are required cell autonomously to restrict CM specification and promote endothelial cell (EC) specification, which is overtly similar to the ability of Wnt signaling to direct a transformation between these progenitors in embryonic stem cells. Therefore, these results argue that during anterior–posterior patterning of the mesoderm Tcf7l1 proteins are cell autonomously required to limit Wnt signaling, which balances CM and EC progenitor specification within the anterior lateral plate mesoderm. This study expands our understanding of the in vivo developmental requirements of Tcf7l1 proteins and the mechanisms directing CM development in vertebrates.

Genes / Markers
Figures
Figure Gallery (13 images) / 2
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
f2TgTransgenic Insertion
    s843TgTransgenic Insertion
      w32TgTransgenic Insertion
        1 - 3 of 3
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        Human Disease / Model
        No data available
        Sequence Targeting Reagents
        Target Reagent Reagent Type
        tcf7l1aMO1-tcf7l1aMRPHLNO
        tcf7l1bMO1-tcf7l1bMRPHLNO
        tp53MO4-tp53MRPHLNO
        1 - 3 of 3
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        Fish
        Antibodies
        Name Type Antigen Genes Isotypes Host Organism
        Ab-MF20monoclonal
          IgG2bMouse
          Ab-S46monoclonalIgG1Mouse
          1 - 2 of 2
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          Orthology
          No data available
          Engineered Foreign Genes
          Marker Marker Type Name
          DsRed2EFGDsRed2
          EGFPEFGEGFP
          GFPEFGGFP
          1 - 3 of 3
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          Mapping
          No data available