Isl1-expressing non-venous cell lineage contributes to cardiac lymphatic vessel development

Dev Biol. 2019 Aug 15;452(2):134-143. doi: 10.1016/j.ydbio.2019.05.002. Epub 2019 May 18.


The origin of the mammalian lymphatic vasculature has been studied for more than a century; however, details regarding organ-specific lymphatic development remain unknown. A recent study reported that cardiac lymphatic endothelial cells (LECs) stem from venous and non-venous origins in mice. Here, we identified Isl1-expressing progenitors as a potential non-venous origin of cardiac LECs. Genetic lineage tracing with Isl1-Cre reporter mice suggested a possible contribution from the Isl1-expressing pharyngeal mesoderm constituting the second heart field to lymphatic vessels around the cardiac outflow tract as well as to those in the facial skin and the lymph sac. Isl1+ lineage-specific deletion of Prox1 resulted in disrupted LYVE1+ vessel structures, indicating a Prox1-dependent mechanism in this contribution. Tracing back to earlier embryonic stages revealed the presence of VEGFR3+ and/or Prox1+ cells that overlapped with the Isl1+ pharyngeal core mesoderm. These data may provide insights into the developmental basis of heart diseases involving lymphatic vasculature and improve our understanding of organ-based lymphangiogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Lineage*
  • Endothelial Cells / metabolism
  • Heart / embryology*
  • Homeodomain Proteins / metabolism
  • LIM-Homeodomain Proteins / metabolism*
  • Lymphangiogenesis*
  • Lymphatic Vessels / cytology*
  • Lymphatic Vessels / embryology*
  • Mesoderm / embryology
  • Mesoderm / metabolism
  • Mice
  • Pharynx / cytology
  • Stem Cells / metabolism
  • Transcription Factors / metabolism*
  • Tumor Suppressor Proteins / metabolism
  • Vascular Endothelial Growth Factor Receptor-3 / metabolism


  • Homeodomain Proteins
  • LIM-Homeodomain Proteins
  • Transcription Factors
  • Tumor Suppressor Proteins
  • insulin gene enhancer binding protein Isl-1
  • prospero-related homeobox 1 protein
  • Vascular Endothelial Growth Factor Receptor-3