Format

Send to

Choose Destination
See comment in PubMed Commons below
Cell Rep. 2015 Feb 24;10(7):1158-72. doi: 10.1016/j.celrep.2015.01.049. Epub 2015 Feb 19.

Vascular endothelial growth factor receptor 3 controls neural stem cell activation in mice and humans.

Author information

1
Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06510-3221, USA.
2
Université Pierre and Marie Curie-Paris 6, Groupe Hospitalier Pitié-Salpètrière, 75013 Paris, France; INSERM/CNRS U-1127/UMR-7225, Groupe Hospitalier Pitié-Salpètrière, 75013 Paris, France; APHP, Groupe Hospitalier Pitié-Salpètrière, 75013 Paris, France.
3
Department of Neurology, Yale University School of Medicine, New Haven, CT 06510-3221, USA.
4
Department of Genetics, Yale University School of Medicine, New Haven, CT 06510-3221, USA.
5
Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06510-3221, USA.
6
Wihuri Research Institute and Translational Cancer Biology Program, Biomedicum Helsinki, University of Helsinki, 00014 Helsinki, Finland.
7
Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06510-3221, USA. Electronic address: anne.eichmann@yale.edu.
8
Université Pierre and Marie Curie-Paris 6, Groupe Hospitalier Pitié-Salpètrière, 75013 Paris, France; INSERM/CNRS U-1127/UMR-7225, Groupe Hospitalier Pitié-Salpètrière, 75013 Paris, France; APHP, Groupe Hospitalier Pitié-Salpètrière, 75013 Paris, France; Department of Neurology, Yale University School of Medicine, New Haven, CT 06510-3221, USA. Electronic address: jean-leon.thomas@yale.edu.

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.

PMID:
25704818
PMCID:
PMC4685253
DOI:
10.1016/j.celrep.2015.01.049
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Support Center