PUBLICATION

Hemodynamic-mediated endocardial signaling controls in vivo myocardial reprogramming

Authors
Gálvez-Santisteban, M., Chen, D., Zhang, R., Serrano, R., Nguyen, C., Zhao, L., Nerb, L., Masutani, E.M., Vermot, J., Burns, C.G., Burns, C.E., Del Álamo, J.C., Chi, N.C.
ID
ZDB-PUB-190627-8
Date
2019
Source
eLIFE   8: (Journal)
Registered Authors
Burns (Erter), Caroline, Chi, Neil C., Vermot, Julien, Zhang, Ruilin, Zhao, Long
Keywords
developmental biology, genetics, heart, hemodynamics, regeneration, reprogramming, zebrafish
MeSH Terms
  • Mechanotransduction, Cellular*
  • TRPV Cation Channels/metabolism
  • Animals
  • Heart Injuries/pathology*
  • Zebrafish
  • Receptors, Notch/metabolism
  • Endocardium/physiology*
  • Hemodynamics*
  • Myocytes, Cardiac/physiology*
  • Kruppel-Like Transcription Factors/metabolism
  • Zebrafish Proteins/metabolism
  • Regeneration*
(all 12)
PubMed
31237233 Full text @ Elife
Abstract
Lower vertebrate and neonatal mammalian hearts exhibit the remarkable capacity to regenerate through the reprogramming of pre-existing cardiomyocytes. However, how cardiac injury initiates signaling pathways controlling this regenerative reprogramming remains to be defined. Here, we utilize in vivo biophysical and genetic fate mapping zebrafish studies to reveal that altered hemodynamic forces due to cardiac injury activate a sequential endocardial-myocardial signaling cascade to direct cardiomyocyte reprogramming and heart regeneration. Specifically, these altered forces are sensed by the endocardium through the mechanosensitive channel Trpv4 to control Klf2a transcription factor expression. Consequently, Klf2a then activates endocardial Notch signaling which results in the non-cell autonomous initiation of myocardial Erbb2 and BMP signaling to promote cardiomyocyte reprogramming and heart regeneration. Overall, these findings not only reveal how the heart senses and adaptively responds to environmental changes due to cardiac injury, but also provide insight into how flow-mediated mechanisms may regulate cardiomyocyte reprogramming and heart regeneration.
Genes / Markers
Figures
Figure Gallery (19 images) / 2
Show all Figures
Expression
Gene Antibody Fish Conditions Stage Qualifier Anatomy Assay Figure
bmp10s957Tgchemical ablation: cardiac ventricle, chemical treatment by environment: blebbistatin, chemical treatment by environment: metronidazoleDays 7-13ISH
bmp10s957Tgchemical ablation: cardiac ventricle, chemical treatment by environment: DAPT, chemical treatment by environment: metronidazoleDays 7-13ISH
bmp10s957Tgchemical ablation: cardiac ventricle, chemical treatment by environment: metronidazoleDays 7-13ISH
d2EGFPgata2aum27/um27; mw43Tg; s957TgcontrolDay 6IFL
d2EGFPgata2aum27/um27; mw43Tg; s957Tgchemical ablation: cardiac ventricle, chemical treatment by environment: metronidazoleDay 6IFL
d2EGFPklf2aig4/ig4; mw43Tg; s957Tgchemical ablation: cardiac ventricle, chemical treatment by environment: metronidazoleDay 6IFL
d2EGFPmw30Tg; s957Tgchemical ablation: cardiac ventricle, chemical treatment by environment: blebbistatin, chemical treatment by environment: metronidazoleDays 7-13IFL
d2EGFPmw30Tg; s957Tgchemical ablation: cardiac ventricle, chemical treatment by environment: DAPT, chemical treatment by environment: metronidazoleDays 7-13IFL
d2EGFPmw30Tg; s957Tgchemical ablation: cardiac ventricle, chemical treatment by environment: metronidazoleDays 7-13IFL
d2EGFPmw43Tg; s896Tg; s957Tgchemical ablation: cardiac ventricle, chemical treatment by environment: metronidazoleDay 6IFL
1 - 10 of 72
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Phenotype
Fish Conditions Stage Phenotype Figure
erbb2st50/st50; s957Tgchemical ablation: cardiac ventricle, chemical treatment by environment: metronidazoleDays 7-13
erbb2st50/st50; s957Tgchemical ablation: cardiac ventricle, chemical treatment by environment: metronidazoleDays 7-13
erbb2st50/st50; s957Tgchemical ablation: cardiac ventricle, chemical treatment by environment: metronidazoleDays 7-13
fb11Tg; fb2Tg; s957Tg; sd20Tgchemical ablation: cardiac ventricle, chemical treatment by environment: metronidazole, chemical treatment by environment: tamoxifenDays 7-13
fb11Tg; fb2Tg; s957Tg; sd20Tgchemical ablation: cardiac ventricle, heat shock, chemical treatment by environment: metronidazole, chemical treatment by environment: tamoxifenDays 7-13
fb11Tg; s957Tgchemical ablation: cardiac ventricle, heat shock, chemical treatment by environment: metronidazoleDays 7-13
fb11Tg; s957Tgchemical ablation: cardiac ventricle, heat shock, chemical treatment by environment: metronidazoleDays 7-13
fb11Tg; s957Tgchemical ablation: cardiac ventricle, heat shock, chemical treatment by environment: metronidazoleDays 7-13
fb24Tg; s898Tg; s957Tgchemical ablation: cardiac ventricle, heat shock, chemical treatment by environment: metronidazole, chemical treatment by environment: tamoxifenDays 7-13
fb24Tg; s898Tg; s957Tgchemical ablation: cardiac ventricle, heat shock, chemical treatment by environment: metronidazole, chemical treatment by environment: tamoxifenDays 7-13
1 - 10 of 97
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Mutations / Transgenics
Allele Construct Type Affected Genomic Region
fb2TgTransgenic Insertion
    fb11TgTransgenic Insertion
      fb24TgTransgenic Insertion
        ig4
          		Indel
          ig11TgTransgenic Insertion
            jh11TgTransgenic Insertion
              mss5TgTransgenic Insertion
                mw30TgTransgenic Insertion
                  mw43TgTransgenic Insertion
                    pd10TgTransgenic Insertion
                      1 - 10 of 19
                      Show
                      Human Disease / Model
                      No data available
                      Sequence Targeting Reagents
                      No data available
                      Fish
                      Fish
                      erbb2st50/st50; s957Tg
                      fb11Tg; fb2Tg; s957Tg; sd20Tg
                      fb11Tg; s957Tg
                      fb24Tg; s898Tg; s957Tg
                      gata2aum27/um27; ig11Tg; s957Tg
                      gata2aum27/um27; mw43Tg; s957Tg
                      gata2aum27/um27; s957Tg
                      ig11Tg; s957Tg
                      klf2aig4/ig4; mw43Tg; s957Tg
                      klf2aig4/ig4; s957Tg
                      1 - 10 of 17
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                      Antibodies
                      Name Type Antigen Genes Isotypes Host Organism
                      Ab-MF20monoclonal
                        		IgG2bMouse
                        1 - 1 of 1
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                        Orthology
                        No data available
                        Engineered Foreign Genes
                        Marker Marker Type Name
                        AmCyanEFGAmCyan
                        CeruleanEFGCerulean
                        CreEFGCre
                        d2EGFPEFGd2EGFP
                        DsRedEFGDsRed
                        EGFPEFGEGFP
                        GFPEFGGFP
                        mCherryEFGmCherry
                        mKate2EFGmKate2
                        ZsYellowEFGZsYellow
                        1 - 10 of 10
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                        Mapping
                        No data available
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                        Citation
                        Gálvez-Santisteban, M., Chen, D., Zhang, R., Serrano, R., Nguyen, C., Zhao, L., Nerb, L., Masutani, E.M., Vermot, J., Burns, C.G., Burns, C.E., Del Álamo, J.C., Chi, N.C. (2019) Hemodynamic-mediated endocardial signaling controls in vivo myocardial reprogramming. eLIFE. 8:.