An Endogenous Vitamin K-Dependent Mechanism Regulates Cell Proliferation in the Brain Subventricular Stem Cell Niche

• DOI: 10.1002/stem.1045
• Publication Date: 2012-01-30T20:48:33Z
• Authors: Aurore Gely-Pernot; Valérie Coronas; Thomas Harnois; Laetitia Prestoz; Nathalie Mandairon; Anne Didier; Jean Marc Berjeaud; Arnaud Monvoisin; Nicolas Bourmeyster; Pablo García De F...; Michel Philippe; Omar Benzakour
• Keywords: GAS6

Neural stem cells (NSC) persist in the adult mammalian brain, within subventricular zone (SVZ). The endogenous mechanisms underpinning SVZ and progenitor cell proliferation are not fully elucidated. Vitamin K-dependent proteins (VKDPs) mainly secreted factors that were initially discovered as major regulators of blood coagulation. Warfarin ((S(-)-3-acetonylbenzyl)-4-hydroxycoumarin)), a widespread anticoagulant, is vitamin K antagonist inhibits production functional VKDP. We demonstrate suppression VKDPs production, vitro, by exposure cultures to warfarin or, vivo, its intracerebroventricular injection mice, leads substantial increase proliferation. identify anticoagulant factors, protein S structural homolog Gas6, two only produced describe expression activation pattern their Tyro3, Axl, Mer tyrosine kinase receptors. Both vitro vivo loss function studies consisting either Gas6 gene invalidation or neutralization, provided evidence for an important novel regulatory role these neurogenic niche. Specifically, we show while reduction numbers stem-like olfactory bulb neurogenesis, Our study opens up new perspectives investigating further K, VKDPs, anticoagulants NSC biology health disease.