PUBLICATION

Differential vegfc expression dictates lymphatic response during zebrafish heart development and regeneration

Authors
Duca, S., Xia, Y., Elmagid, L.A., Bakis, I., Qiu, M., Cao, Y., Guo, Y., Eichenbaum, J.V., McCain, M.L., Kang, J., Harrison, M.R.M., Cao, J.
ID
ZDB-PUB-241114-50
Date
2024
Source
Development (Cambridge, England)   151(22): (Journal)
Registered Authors
Cao, Jingli, Harrison, Michael, Kang, Junsu
Keywords
Coronary artery, Heart regeneration, Lymphatic vessel, Thrombocytes, Vegfc, Zebrafish
MeSH Terms
  • Vascular Endothelial Growth Factor C*/genetics
  • Vascular Endothelial Growth Factor C*/metabolism
  • Regeneration*/physiology
  • Gene Expression Regulation, Developmental
  • Animals, Genetically Modified
  • Zebrafish Proteins*/genetics
  • Zebrafish Proteins*/metabolism
  • Zebrafish*
  • Blood Platelets/metabolism
  • Coronary Vessels/metabolism
  • Animals
  • Heart*/physiology
  • Cell Proliferation
  • Myocytes, Cardiac/metabolism
  • Lymphatic Vessels/metabolism
  • Lymphangiogenesis*/genetics
(all 16)
PubMed
39514676 Full text @ Development
Abstract
Vascular endothelial growth factor C (Vegfc) is crucial for lymphatic and blood vessel development, yet its cellular sources and specific functions in heart development remain unclear. To address this, we created a vegfc reporter and an inducible overexpression line in zebrafish. We found vegfc expression in large coronary arteries, circulating thrombocytes, cardiac adipocytes, and outflow tract smooth muscle cells. Notably, while coronary lymphangiogenesis aligns with Vegfc-expressing arteries in juveniles, it occurs only after coronary artery formation. Vegfc overexpression induced ectopic lymphatics on the ventricular surface prior to arterial formation, indicating that Vegfc abundance, rather than arterial presence, drives lymphatic development. However, this overexpression did not affect coronary artery coverage, suggesting a specific role for Vegfc in lymphatic, rather than arterial, development. Thrombocytes emerged as the initial Vegfc source during inflammation following heart injuries, transitioning to endocardial and myocardial expression during regeneration. Lower Vegfc levels in the amputation model corresponded with a lack of lymphatic expansion. Importantly, Vegfc overexpression enhanced lymphatic expansion and promoted scar resolution without affecting cardiomyocyte proliferation, highlighting its role in regulating lymphangiogenesis and promoting heart regeneration.
Errata / Notes
This article is corrected by ZDB-PUB-250411-2.
Genes / Markers
Figures
No images available
Expression
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
f2TgTransgenic Insertion
    hu5333TgTransgenic Insertion
      hu7135TgTransgenic Insertion
        nz50TgTransgenic Insertion
          nz101TgTransgenic Insertion
            pd13TgTransgenic Insertion
              pd36TgTransgenic Insertion
                pd42TgTransgenic Insertion
                  wcm111TgTransgenic Insertion
                    wcm112TgTransgenic Insertion
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                      Human Disease / Model
                      Sequence Targeting Reagents
                      Fish
                      Antibodies
                      Orthology
                      Engineered Foreign Genes
                      Marker Marker Type Name
                      BFPEFGBFP
                      CitrineEFGCitrine
                      CreEFGCre
                      DipToxEFGDipTox
                      DsRedEFGDsRed
                      DsRed2EFGDsRed2
                      EGFPEFGEGFP
                      mCherryEFGmCherry
                      NTREFGNTR
                      RFPEFGRFP
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                      Mapping