Lineage tracing demonstrates the venous origin of the mammalian lymphatic vasculature

R. Sathish Srinivasan, Miriam E. Dillard, Oleg V. Lagutin, Fu Jung Lin, Sophia Tsai, Ming Jer Tsai, Igor M. Samokhvalov, Guillermo Oliver*

*Corresponding author for this work

Research output: Contribution to journalArticle

331 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)2422-2432
Number of pages11
JournalGenes and Development
Issue number19
StatePublished - Oct 1 2007


  • Lineage tracing
  • Lymphangiogenesis
  • Lymphatic endothelial cells
  • Mouse
  • Prox1
  • Runx1

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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