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  • The EMBO Journal (2002) 21, 1505 - 1513
  • doi:10.1093/emboj/21.7.1505

An essential role for Prox1 in the induction of the lymphatic endothelial cell phenotype

Jeffrey T. Wigle1,2, Natasha Harvey1, Michael Detmar3, Irina Lagutina1, Gerard Grosveld1, Michael D. Gunn4, David G. Jackson5 and Guillermo Oliver1

  1. Department of Genetics, St Jude Children's Research Hospital, Memphis, TN 38105, USA
  2. Present address: Division of Stroke and Vascular Disease and Department of Biochemistry and Medical Genetics, St Boniface General Hospital Research Centre, Winnipeg, Canada
  3. Cutaneous Biology Research Center and Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
  4. Division of Cardiology, Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA
  5. MRC Human Immunology Unit, Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford OX3 9DS, UK

Correspondence to:

Guillermo Oliver, E-mail: guillermo.oliver@stjude.org

Received 17 December 2001; Accepted 31 January 2002; Revised 22 January 2002

The process of angiogenesis has been well documented, but little is known about the biology of lymphatic endothelial cells and the molecular mechanisms controlling lymphangiogenesis. The homeobox gene Prox1 is expressed in a subpopulation of endothelial cells that, after budding from veins, gives rise to the mammalian lymphatic system. In Prox1-/- embryos, this budding becomes arrested at around embryonic day (E)11.5, resulting in embryos without lymphatic vasculature. Unlike the endothelial cells that bud off in E11.5 wild-type embryos, those of Prox1-null embryos did not co-express any lymphatic markers such as VEGFR-3, LYVE-1 or SLC. Instead, the mutant cells appeared to have a blood vascular phenotype, as determined by their expression of laminin and CD34. These results suggest that Prox1 activity is required for both maintenance of the budding of the venous endothelial cells and differentiation toward the lymphatic phenotype. On the basis of our findings, we propose that a blood vascular phenotype is the default fate of budding embryonic venous endothelial cells; upon expression of Prox1, these budding cells adopt a lymphatic vasculature phenotype.

  • Keywords:

    • lymphangiogenesis,
    • lymphatic endothelial cells,
    • LYVE-1,
    • Prox1,
    • SLC,
    • VEGFR-3