title: Lineage tracing demonstrates the venous origin of the mammalian lymphatic vasculature.
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.
authors.affiliation: Department of Genetics and Tumor Cell Biology, St. Jude Children's Hospital, Memphis, Tennessee 38105, USA.
authors.forename: R Sathish
authors.initials: RS
authors.lastname: Srinivasan
authors.forename: Miriam E
authors.initials: ME
authors.lastname: Dillard
authors.forename: Oleg V
authors.initials: OV
authors.lastname: Lagutin
authors.forename: Fu-Jung
authors.initials: FJ
authors.lastname: Lin
authors.forename: Sophia
authors.initials: S
authors.lastname: Tsai
authors.forename: Ming-Jer
authors.initials: MJ
authors.lastname: Tsai
authors.forename: Igor M
authors.initials: IM
authors.lastname: Samokhvalov
authors.forename: Guillermo
authors.initials: G
authors.lastname: Oliver
mesh_terms: D000818:Animals; D019070:Cell Lineage; D002465:Cell Movement; D049109:Cell Proliferation; D050676:Core Binding Factor Alpha 2 Subunit / Q000032:analysis / Q000235:genetics; D004628:Embryonic Structures / Q000737:chemistry / Q000166:cytology / Q000187:drug effects; D042783:Endothelial Cells / Q000166:cytology* / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000502:physiology; D018398:Homeodomain Proteins / Q000032:analysis / Q000235:genetics; D019426:Integrases / Q000235:genetics; D042601:Lymphatic Vessels / Q000196:embryology*; D051379:Mice; D008822:Mice, Transgenic; D042787:Receptor, TIE-2 / Q000032:analysis / Q000235:genetics; D013629:Tamoxifen / Q000494:pharmacology; D025521:Tumor Suppressor Proteins / Q000032:analysis / Q000235:genetics; D014680:Veins / Q000166:cytology* / Q000196:embryology; D000098551:Prospero-Related Homeobox 1 Protein
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D018398:Homeodomain Proteins; D025521:Tumor Suppressor Proteins; D000098551:Prospero-Related Homeobox 1 Protein; D013629:Tamoxifen; D042787:Receptor, TIE-2; C045073:Cre recombinase; D019426:Integrases