PUBLICATION

Identification and functional characterization of cardiac pacemaker cells in zebrafish

Authors
Tessadori, F., van Weerd, J.H., Burkhard, S.B., Verkerk, A.O., de Pater, E., Boukens, B.J., Vink, A., Christoffels, V.M., and Bakkers, J.
ID
ZDB-PUB-121030-16
Date
2012
Source
PLoS One   7(10): e47644 (Journal)
Registered Authors
Bakkers, Jeroen
Keywords
none
MeSH Terms
  • Animals
  • Embryonic Development
  • Gene Expression Regulation, Developmental*
  • Heart/embryology
  • Heart Atria/metabolism
  • LIM-Homeodomain Proteins*/genetics
  • LIM-Homeodomain Proteins*/metabolism
  • Myocardial Contraction*
  • Myocytes, Cardiac/cytology
  • Myocytes, Cardiac/metabolism
  • Sinoatrial Node/cytology
  • T-Box Domain Proteins*/genetics
  • T-Box Domain Proteins*/metabolism
  • Transcription Factors*/genetics
  • Transcription Factors*/metabolism
  • Zebrafish
  • Zebrafish Proteins*/genetics
  • Zebrafish Proteins*/metabolism
(all 18)
PubMed
23077655 Full text @ PLoS One
Abstract

In the mammalian heart a conduction system of nodes and conducting cells generates and transduces the electrical signals evoking myocardial contractions. Specialized pacemaker cells initiating and controlling cardiac contraction rhythmicity are localized in an anatomically identifiable structure of myocardial origin, the sinus node. We previously showed that in mammalian embryos sinus node cells originate from cardiac progenitors expressing the transcription factors T-box transcription factor 3 (Tbx3) and Islet-1 (Isl1). Although cardiac development and function are strikingly conserved amongst animal classes, in lower vertebrates neither structural nor molecular distinguishable components of a conduction system have been identified, questioning its evolutionary origin. Here we show that zebrafish embryos lacking the LIM/homeodomain-containing transcription factor Isl1 display heart rate defects related to pacemaker dysfunction. Moreover, 3D reconstructions of gene expression patterns in the embryonic and adult zebrafish heart led us to uncover a previously unidentified, Isl1-positive and Tbx2b-positive region in the myocardium at the junction of the sinus venosus and atrium. Through their long interconnecting cellular protrusions the identified Isl1-positive cells form a ring-shaped structure. In vivo labeling of the Isl1-positive cells by transgenic technology allowed their isolation and electrophysiological characterization, revealing their unique pacemaker activity. In conclusion we demonstrate that Isl1-expressing cells, organized as a ring-shaped structure around the venous pole, hold the pacemaker function in the adult zebrafish heart. We have thereby identified an evolutionary conserved, structural and molecular distinguishable component of the cardiac conduction system in a lower vertebrate.

Genes / Markers
Marker Marker Type Name
bmp4GENEbone morphogenetic protein 4
hcn4GENEhyperpolarization activated cyclic nucleotide-gated potassium channel 4
isl1aGENEISL LIM homeobox 1a
myl7GENEmyosin, light chain 7, regulatory
nppaGENEnatriuretic peptide A
tbx2bGENET-box transcription factor 2b
1 - 6 of 6
Show
Figures
Figure Gallery (9 images)
Show all Figures
Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
hu6635TgTransgenic Insertion
    nkuasgfp1aTgTransgenic Insertion
      nkuasrfp1aTgTransgenic Insertion
        sa29
          Point Mutation
          twu34TgTransgenic Insertion
            1 - 5 of 5
            Show
            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
            EGFPEFGEGFP
            GAL4FFEFGGAL4FF
            RFPEFGRFP
            1 - 3 of 3
            Show
            Mapping
            No data available