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

Jeffrey T. Wigle, Natasha Harvey, Michael Detmar, Irina Lagutina, Gerard Grosveld, Michael D. Gunn, David G. Jackson, Guillermo Oliver

Research output: Contribution to journalArticlepeer-review

642 Scopus citations

Abstract

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 Proxl 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 Proxl-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 Proxl, these budding cells adopt a lymphatic vasculature phenotype.

Original languageEnglish (US)
Pages (from-to)1505-1513
Number of pages9
JournalEMBO Journal
Volume21
Issue number7
DOIs
StatePublished - Apr 2 2002

Keywords

  • LYVE-1
  • Lymphangiogenesis
  • Lymphatic endothelial cells
  • Prox1
  • SLC
  • VEGFR-3

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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