Vascular Endothelial Growth Factor Receptor 3 Controls Neural Stem Cell Activation in Mice and Humans

Overview

Journal Cell Rep

Publisher Cell Press

Specialties Biology
Cell Biology
Molecular Biology

Date 2015 Feb 24

PMID 25704818

Citations 55

Authors

Jinah Han

Charles-Felix Calvo

Tae Hyuk Kang

Kasey L Baker

June-Hee Park

Carlos Parras

Marine Levittas

Ulrick Birba

Laurence Pibouin-Fragner

Pascal Fragner

Kaya Bilguvar

Ronald S Duman

Harri Nurmi

Kari Alitalo

Anne C Eichmann

Jean-Leon Thomas

Affiliations

Soon will be listed here.

Abstract

Neural stem cells (NSCs) continuously produce new neurons within the adult mammalian hippocampus. NSCs are typically quiescent but activated to self-renew or differentiate into neural progenitor cells. The molecular mechanisms of NSC activation remain poorly understood. Here, we show that adult hippocampal NSCs express vascular endothelial growth factor receptor (VEGFR) 3 and its ligand VEGF-C, which activates quiescent NSCs to enter the cell cycle and generate progenitor cells. Hippocampal NSC activation and neurogenesis are impaired by conditional deletion of Vegfr3 in NSCs. Functionally, this is associated with compromised NSC activation in response to VEGF-C and physical activity. In NSCs derived from human embryonic stem cells (hESCs), VEGF-C/VEGFR3 mediates intracellular activation of AKT and ERK pathways that control cell fate and proliferation. These findings identify VEGF-C/VEGFR3 signaling as a specific regulator of NSC activation and neurogenesis in mammals.

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