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Vascular Cell

, 6:9

Lymphatics in Health and Disease

Abstract

BackgroundDicer 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.

MethodsIn 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.

ResultsWe show that cell-specific inactivation of dicer in Tie2 expressing cells does not perturb early blood vessel development and patterning. Tie2-Cre; dicer mutant embryos do not show any blood vascular defects until embryonic day E12.5, 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.

ConclusionThus, 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.

KeywordsDicer Lymphangiogenesis Veino-lymphatic separation Angiogenesis RNA interference AbbreviationsCLEC-2C-type lectin-like receptor 2

CvCardinal vein

EEmbryonic day

IcaInternal carotid artery

LsLymph sac

miRNAmicroRNA

mRNAMessenger RNA

Pecam-1Platelet endothelial cell adhesion molecule 1

siRNAShort interfering RNA

Vegfr-3Vascular endothelial growth factor receptor 3

WTWild type.

Electronic supplementary materialThe online version of this article doi:10.1186-2045-824X-6-9 contains supplementary material, which is available to authorized users.

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Autor: Sébastien Gauvrit - Josette Philippe - Matthieu Lesage - Marc Tjwa - Isabelle Godin - Stéphane Germain

Fuente: https://link.springer.com/article/10.1186/2045-824X-6-9



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