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

First Author  Han J Year  2015
Journal  Cell Rep Volume  10
Issue  7 Pages  1158-72
PubMed ID  25704818 Mgi Jnum  J:224173
Mgi Id  MGI:5661633 Doi  10.1016/j.celrep.2015.01.049
Citation  Han J, et al. (2015) Vascular endothelial growth factor receptor 3 controls neural stem cell activation in mice and humans. Cell Rep 10(7):1158-72
abstractText  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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