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Vascular endothelial growth factor directly inhibits primitive neural stem cell survival but promotes definitive neural stem cell survival

T Wada, Jody Haigh, M Ema, S Hitoshi, R Chaddah, J Rossant, A Nagy and D van der Kooy (2006) JOURNAL OF NEUROSCIENCE. 26(25). p.6803-6812
abstract
There are two types of neural stem cells (NSCs). Primitive NSCs [leukemia inhibitory factor (LIF) dependent but exogenous fibroblast growth factor (FGF) 2 independent] can be derived from mouse embryonic stem (ES) cells in vitro and from embryonic day 5.5 (E5.5) to E7.5 epiblast and E7.5-E8.5 neuroectoderm in vivo. Definitive NSCs (LIF independent but FGF2 dependent) first appear in the E8.5 neural plate and persist throughout life. Primitive NSCs give rise to definitive NSCs. Loss and gain of functions were used to study the role of vascular endothelial growth factor (VEGF)-A and its receptor, Flk1, in NSCs. The numbers of Flk1 knock-out mice embryo-derived and ES cell-derived primitive NSCs were increased because of the enhanced survival of primitive NSCs. In contrast, neural precursor-specific, Flk1 conditional knock-out mice-derived, definitive NSCs numbers were decreased because of the enhanced cell death of definitive NSCs. These effects were not observed in cells lacking Flt1, another VEGF receptor. In addition, the cell death stimulated by VEGF-A of primitive NSC and the cell survival stimulated by VEGF-A of definitive NSC were blocked by Flk1/Fc-soluble receptors and VEGF-A function-blocking antibodies. These VEGF-A phenotypes also were blocked by inhibition of the downstream effector nuclear factor kappa B (NF-kappa B). Thus, both the cell death of primitive NSC and the cell survival of definitive NSC induced by VEGF-A stimulation are mediated by bifunctional NF-kappa B effects. In conclusion, VEGF-A function through Flk1 mediates survival (and not proliferative or fate change) effects on NSCs, specifically.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
ADULT HIPPOCAMPAL NEUROGENESIS, NF-KAPPA-B, IN-VIVO, STIMULATES NEUROGENESIS, TRANSCRIPTION FACTORS, VEGF, EXPRESSION, MOUSE, MICE, APOPTOSIS, neural stem cell, embryonic stem cell, VEGF-A, cell survival/death, neurosphere, NF-kappa B
journal title
JOURNAL OF NEUROSCIENCE
J. Neurosci.
volume
26
issue
25
pages
6803 - 6812
Web of Science type
Article
Web of Science id
000238473600017
JCR category
NEUROSCIENCES
JCR impact factor
7.453 (2006)
JCR rank
15/199 (2006)
JCR quartile
1 (2006)
ISSN
0270-6474
DOI
10.1523/JNEUROSCI.0526-06.2006
language
English
UGent publication?
no
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
1202219
handle
http://hdl.handle.net/1854/LU-1202219
date created
2011-04-05 11:49:55
date last changed
2016-12-19 15:39:35
@article{1202219,
  abstract     = {There are two types of neural stem cells (NSCs). Primitive NSCs [leukemia inhibitory factor (LIF) dependent but exogenous fibroblast growth factor (FGF) 2 independent] can be derived from mouse embryonic stem (ES) cells in vitro and from embryonic day 5.5 (E5.5) to E7.5 epiblast and E7.5-E8.5 neuroectoderm in vivo. Definitive NSCs (LIF independent but FGF2 dependent) first appear in the E8.5 neural plate and persist throughout life. Primitive NSCs give rise to definitive NSCs. Loss and gain of functions were used to study the role of vascular endothelial growth factor (VEGF)-A and its receptor, Flk1, in NSCs. The numbers of Flk1 knock-out mice embryo-derived and ES cell-derived primitive NSCs were increased because of the enhanced survival of primitive NSCs. In contrast, neural precursor-specific, Flk1 conditional knock-out mice-derived, definitive NSCs numbers were decreased because of the enhanced cell death of definitive NSCs. These effects were not observed in cells lacking Flt1, another VEGF receptor. In addition, the cell death stimulated by VEGF-A of primitive NSC and the cell survival stimulated by VEGF-A of definitive NSC were blocked by Flk1/Fc-soluble receptors and VEGF-A function-blocking antibodies. These VEGF-A phenotypes also were blocked by inhibition of the downstream effector nuclear factor kappa B (NF-kappa B). Thus, both the cell death of primitive NSC and the cell survival of definitive NSC induced by VEGF-A stimulation are mediated by bifunctional NF-kappa B effects. In conclusion, VEGF-A function through Flk1 mediates survival (and not proliferative or fate change) effects on NSCs, specifically.},
  author       = {Wada, T and Haigh, Jody and Ema, M and Hitoshi, S and Chaddah, R and Rossant, J and Nagy, A and van der Kooy, D},
  issn         = {0270-6474},
  journal      = {JOURNAL OF NEUROSCIENCE},
  keyword      = {ADULT HIPPOCAMPAL NEUROGENESIS,NF-KAPPA-B,IN-VIVO,STIMULATES NEUROGENESIS,TRANSCRIPTION FACTORS,VEGF,EXPRESSION,MOUSE,MICE,APOPTOSIS,neural stem cell,embryonic stem cell,VEGF-A,cell survival/death,neurosphere,NF-kappa B},
  language     = {eng},
  number       = {25},
  pages        = {6803--6812},
  title        = {Vascular endothelial growth factor directly inhibits primitive neural stem cell survival but promotes definitive neural stem cell survival},
  url          = {http://dx.doi.org/10.1523/JNEUROSCI.0526-06.2006},
  volume       = {26},
  year         = {2006},
}

Chicago
Wada, T, Jody Haigh, M Ema, S Hitoshi, R Chaddah, J Rossant, A Nagy, and D van der Kooy. 2006. “Vascular Endothelial Growth Factor Directly Inhibits Primitive Neural Stem Cell Survival but Promotes Definitive Neural Stem Cell Survival.” Journal of Neuroscience 26 (25): 6803–6812.
APA
Wada, T., Haigh, J., Ema, M., Hitoshi, S., Chaddah, R., Rossant, J., Nagy, A., et al. (2006). Vascular endothelial growth factor directly inhibits primitive neural stem cell survival but promotes definitive neural stem cell survival. JOURNAL OF NEUROSCIENCE, 26(25), 6803–6812.
Vancouver
1.
Wada T, Haigh J, Ema M, Hitoshi S, Chaddah R, Rossant J, et al. Vascular endothelial growth factor directly inhibits primitive neural stem cell survival but promotes definitive neural stem cell survival. JOURNAL OF NEUROSCIENCE. 2006;26(25):6803–12.
MLA
Wada, T, Jody Haigh, M Ema, et al. “Vascular Endothelial Growth Factor Directly Inhibits Primitive Neural Stem Cell Survival but Promotes Definitive Neural Stem Cell Survival.” JOURNAL OF NEUROSCIENCE 26.25 (2006): 6803–6812. Print.