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

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 hipp...

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Main Authors:	Han, Jinah, Calvo, Charles-Félix, Kang, Tae Hyuk, Baker, Kasey L., Park, June-Hee, Parras, Carlos, Levittas, Marine, Birba, Ulrick, Pibouin-Fragner, Laurence, Fragner, Pascal, Bilguvar, Kaya, Duman, Ronald S., Nurmi, Harri, Alitalo, Kari, Eichmann, Anne C., Thomas, Jean-Léon
Format:	Online
Language:	English
Published:	2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4685253/

id	pubmed-4685253
recordtype	oai_dc
spelling	pubmed-46852532015-12-21 Vascular Endothelial Growth Factor Receptor 3 Controls Neural Stem Cell Activation in Mice and Humans Han, Jinah Calvo, Charles-Félix Kang, Tae Hyuk Baker, Kasey L. Park, June-Hee Parras, Carlos Levittas, Marine Birba, Ulrick Pibouin-Fragner, Laurence Fragner, Pascal Bilguvar, Kaya Duman, Ronald S. Nurmi, Harri Alitalo, Kari Eichmann, Anne C. Thomas, Jean-Léon Article 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. 2015-02-19 2015-02-24 /pmc/articles/PMC4685253/ /pubmed/25704818 http://dx.doi.org/10.1016/j.celrep.2015.01.049 Text en This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Han, Jinah Calvo, Charles-Félix Kang, Tae Hyuk Baker, Kasey L. Park, June-Hee Parras, Carlos Levittas, Marine Birba, Ulrick Pibouin-Fragner, Laurence Fragner, Pascal Bilguvar, Kaya Duman, Ronald S. Nurmi, Harri Alitalo, Kari Eichmann, Anne C. Thomas, Jean-Léon
spellingShingle	Han, Jinah Calvo, Charles-Félix Kang, Tae Hyuk Baker, Kasey L. Park, June-Hee Parras, Carlos Levittas, Marine Birba, Ulrick Pibouin-Fragner, Laurence Fragner, Pascal Bilguvar, Kaya Duman, Ronald S. Nurmi, Harri Alitalo, Kari Eichmann, Anne C. Thomas, Jean-Léon Vascular Endothelial Growth Factor Receptor 3 Controls Neural Stem Cell Activation in Mice and Humans
author_facet	Han, Jinah Calvo, Charles-Félix Kang, Tae Hyuk Baker, Kasey L. Park, June-Hee Parras, Carlos Levittas, Marine Birba, Ulrick Pibouin-Fragner, Laurence Fragner, Pascal Bilguvar, Kaya Duman, Ronald S. Nurmi, Harri Alitalo, Kari Eichmann, Anne C. Thomas, Jean-Léon
author_sort	Han, Jinah
title	Vascular Endothelial Growth Factor Receptor 3 Controls Neural Stem Cell Activation in Mice and Humans
title_short	Vascular Endothelial Growth Factor Receptor 3 Controls Neural Stem Cell Activation in Mice and Humans
title_full	Vascular Endothelial Growth Factor Receptor 3 Controls Neural Stem Cell Activation in Mice and Humans
title_fullStr	Vascular Endothelial Growth Factor Receptor 3 Controls Neural Stem Cell Activation in Mice and Humans
title_full_unstemmed	Vascular Endothelial Growth Factor Receptor 3 Controls Neural Stem Cell Activation in Mice and Humans
title_sort	vascular endothelial growth factor receptor 3 controls neural stem cell activation in mice and humans
description	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.
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4685253/
_version_	1613514777637683200

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

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