title: The role of RNA interference in the developmental separation of blood and lymphatic vasculature.
abstract: BACKGROUND
  Dicer is an RNase III enzyme that cleaves double stranded RNA and generates functional interfering RNAs that act as important regulators of gene and protein expression. Dicer plays an essential role during mouse development because the deletion of the dicer gene leads to embryonic death. In addition, dicer-dependent interfering RNAs regulate postnatal angiogenesis. However, the role of dicer is not yet fully elucidated during vascular development.
  
  
  METHODS
  In order to explore the functional roles of the RNA interference in vascular biology, we developed a new constitutive Cre/loxP-mediated inactivation of dicer in tie2 expressing cells.
  
  
  RESULTS
  We show that cell-specific inactivation of dicer in Tie2 expressing cells does not perturb early blood vessel development and patterning. Tie2-Cre; dicerfl/fl mutant embryos do not show any blood vascular defects until embryonic day (E)12.5, a time at which hemorrhages and edema appear. Then, midgestational lethality occurs at E14.5 in mutant embryos. The developing lymphatic vessels of dicer-mutant embryos are filled with circulating red blood cells, revealing an impaired separation of blood and lymphatic vasculature.
  
  
  CONCLUSIONS
  Thus, these results show that RNA interference perturbs neither vasculogenesis and developmental angiogenesis, nor lymphatic specification from venous endothelial cells but actually provides evidence for an epigenetic control of separation of blood and lymphatic vasculature.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Gauvrit
authors.forename: Josette
authors.initials: J
authors.lastname: Philippe
authors.forename: Matthieu
authors.initials: M
authors.lastname: Lesage
authors.forename: Marc
authors.initials: M
authors.lastname: Tjwa
authors.forename: Isabelle
authors.initials: I
authors.lastname: Godin
authors.affiliation: Collège de France, Center for Interdisciplinary Research in Biology (CIRB), 11, place Marcelin Berthelot, Paris F-75005, France. stephane.germain@college-de-france.fr.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Germain