PUBLICATION

Hedgehog signaling plays a cell-autonomous role in maximizing cardiac developmental potential

Authors
Thomas, N.A., Koudijs, M., van Eeden, F.J., Joyner, A.L., and Yelon, D.
ID
ZDB-PUB-081022-5
Date
2008
Source
Development (Cambridge, England)   135(22): 3789-3799 (Journal)
Registered Authors
Joyner, Alexandra L., Koudijs, Marco, Yelon, Deborah
Keywords
Hedgehog, Cardiac progenitor specification, Cyclopamine, Heart development, Smoothened, Zebrafish
MeSH Terms
  • Animals
  • Cell Proliferation
  • Mice
  • Endothelial Cells/cytology
  • Myocardium/cytology
  • Myocardium/metabolism*
  • Gene Expression Regulation, Developmental
  • Cell Differentiation
  • Heart/embryology*
  • Signal Transduction*
  • Hedgehog Proteins/genetics
  • Hedgehog Proteins/metabolism*
  • Stem Cells/cytology
  • Stem Cells/metabolism
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish/metabolism
(all 17)
PubMed
18842815 Full text @ Development
Abstract
Elucidation of the complete roster of signals required for myocardial specification is crucial to the future of cardiac regenerative medicine. Prior studies have implicated the Hedgehog (Hh) signaling pathway in the regulation of multiple aspects of heart development. However, our understanding of the contribution of Hh signaling to the initial specification of myocardial progenitor cells remains incomplete. Here, we show that Hh signaling promotes cardiomyocyte formation in zebrafish. Reduced Hh signaling creates a cardiomyocyte deficit, and increased Hh signaling creates a surplus. Through fate-mapping, we find that Hh signaling is required at early stages to ensure specification of the proper number of myocardial progenitors. Genetic inducible fate mapping in mouse indicates that myocardial progenitors respond directly to Hh signals, and transplantation experiments in zebrafish demonstrate that Hh signaling acts cell autonomously to promote the contribution of cells to the myocardium. Thus, Hh signaling plays an essential early role in defining the optimal number of cardiomyocytes, making it an attractive target for manipulation of multipotent progenitor cells.
Genes / Markers
Figures
Figure Gallery (11 images) / 2
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
b577
    Point Mutation
    f2TgTransgenic Insertion
      hi1640TgTransgenic Insertion
      hu1602
        Point Mutation
        tj222
          Point Mutation
          twu277TgTransgenic Insertion
            1 - 6 of 6
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            Human Disease / Model
            No data available
            Sequence Targeting Reagents
            No data available
            Fish
            Antibodies
            Orthology
            No data available
            Engineered Foreign Genes
            Marker Marker Type Name
            DsRed2EFGDsRed2
            EGFPEFGEGFP
            1 - 2 of 2
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            Mapping
            No data available