PUBLICATION

Myocardium and BMP signaling are required for endocardial differentiation

Authors
Palencia-Desai, S., Rost, M.S., Schumacher, J.A., Ton, Q.V., Craig, M.P., Baltrunaite, K., Koenig, A.L., Wang, J., Poss, K.D., Chi, N.C., Stainier, D.Y., Sumanas, S.
ID
ZDB-PUB-150621-2
Date
2015
Source
Development (Cambridge, England)   142(13): 2304-15 (Journal)
Registered Authors
Craig, Michael, Rost, Megan, Schumacher, Jennifer, Stainier, Didier, Sumanas, Saulius, Wang, Jinhu
Keywords
none
MeSH Terms
  • Myocardium/cytology*
  • Myocardium/metabolism*
  • Signal Transduction*
  • Mutation
  • NFATC Transcription Factors/metabolism
  • Animals
  • Heat-Shock Response
  • Zebrafish/embryology*
  • Zebrafish/metabolism
  • Gene Deletion
  • Endocardium/cytology*
  • Endocardium/metabolism*
  • Models, Biological
  • Basic Helix-Loop-Helix Transcription Factors/metabolism
  • Cell Differentiation*
  • Cell Survival
  • Zebrafish Proteins/metabolism
(all 17)
PubMed
26092845 Full text @ Development
Abstract
Endocardial and myocardial progenitors originate in distinct regions of the anterior lateral plate mesoderm and migrate to the midline where they coalesce to form the cardiac tube. Endocardial progenitors acquire a molecular identity distinct from other vascular endothelial cells and initiate expression of specific genes such as nfatc1. Yet the molecular pathways and tissue interactions involved in establishing endocardial identity are poorly understood. The endocardium develops in tight association with cardiomyocytes. To test for a potential role of the myocardium in endocardial morphogenesis, we used two different zebrafish models deficient in cardiomyocytes: the hand2 mutant and a myocardial-specific genetic ablation method. We show that in hand2 mutants endocardial progenitors migrate to the midline but fail to assemble into a cardiac cone and do not express markers of differentiated endocardium. Endocardial differentiation defects were rescued by myocardial but not endocardial-specific expression of hand2. In metronidazole-treated myl7:nitroreductase embryos, myocardial cells were targeted for apoptosis, which resulted in the loss of endocardial nfatc1 expression. However, endocardial cells were present and retained expression of general vascular endothelial markers. We further identified bone morphogenetic protein (BMP) as a candidate myocardium-derived signal required for endocardial differentiation. Chemical and genetic inhibition of BMP signaling at the tailbud stage resulted in severe inhibition of endocardial differentiation while there was little effect on myocardial development. Heat-shock-induced bmp2b expression rescued endocardial nfatc1 expression in hand2 mutants and in myocardium-depleted embryos. Our results indicate that the myocardium is crucial for endocardial morphogenesis and differentiation, and identify BMP as a signal involved in endocardial differentiation.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
ci1TgTransgenic Insertion
    ci8TgTransgenic Insertion
      fr13TgTransgenic Insertion
        m39
          		Deficiency
          pd24TgTransgenic Insertion
            pd65TgTransgenic Insertion
              s6
                		Deficiency
                s843TgTransgenic Insertion
                  s993TgTransgenic Insertion
                    sd7TgTransgenic Insertion
                      1 - 10 of 12
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                      Human Disease / Model
                      No data available
                      Sequence Targeting Reagents
                      Fish
                      Antibodies
                      Orthology
                      Engineered Foreign Genes
                      Marker Marker Type Name
                      EGFPEFGEGFP
                      mCherryEFGmCherry
                      NTREFGNTR
                      1 - 3 of 3
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                      Mapping
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                      Citation
                      Palencia-Desai, S., Rost, M.S., Schumacher, J.A., Ton, Q.V., Craig, M.P., Baltrunaite, K., Koenig, A.L., Wang, J., Poss, K.D., Chi, N.C., Stainier, D.Y., Sumanas, S. (2015) Myocardium and BMP signaling are required for endocardial differentiation. Development (Cambridge, England). 142(13):2304-15.