Lineage tracing demonstrates the venous origin of the mammalian lymphatic vasculature

  1. R. Sathish Srinivasan1,
  2. Miriam E. Dillard1,
  3. Oleg V. Lagutin1,
  4. Fu-Jung Lin2,
  5. Sophia Tsai2,3,
  6. Ming-Jer Tsai2,3,
  7. Igor M. Samokhvalov4, and
  8. Guillermo Oliver1,5
  1. 1 Department of Genetics and Tumor Cell Biology, St. Jude Children’s Hospital, Memphis, Tennessee 38105, USA;
  2. 2 Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA;
  3. 3 Developmental Biology Program, Baylor College of Medicine, Houston, Texas 77030, USA;
  4. 4 Laboratory for Stem Cell Biology, Center for Developmental Biology, RIKEN Kobe, Kobe 650-0047, Japan

Abstract

The origin of the mammalian lymphatic vasculature has been debated for more than 100 years. Whether lymphatic endothelial cells have a single or dual, venous or mesenchymal origin remains controversial. To resolve this debate, we performed Cre/loxP-based lineage-tracing studies using mouse strains expressing Cre recombinase under the control of the Tie2, Runx1, or Prox1 promoter elements. These studies, together with the analysis of Runx1-mutant embryos lacking definitive hematopoiesis, conclusively determined that from venous-derived lymph sacs, lymphatic endothelial cells sprouted, proliferated, and migrated to give rise to the entire lymphatic vasculature, and that hematopoietic cells did not contribute to the developing lymph sacs. We conclude that the mammalian lymphatic system has a solely venous origin.

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