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Brain area-specific effect of TGF-beta signaling on Wnt-dependent neural stem cell expansion

Falk, Sven; Wurdak, Heiko; Ittner, Lars M; Ille, Fabian; Sumara, Grzegorz; Schmid, Marie-Theres; Draganova, Kalina; Lang, Karl S; Paratore, Christian and Levéen, Per LU , et al. (2008) In Cell Stem Cell 2(5). p.472-483
Abstract
Regulating the choice between neural stem cell maintenance versus differentiation determines growth and size of the developing brain. Here we identify TGF-beta signaling as a crucial factor controlling these processes. At early developmental stages, TGF-beta signal activity is localized close to the ventricular surface of the neuroepithelium. In the midbrain, but not in the forebrain, Tgfbr2 ablation results in ectopic expression of Wnt1/beta-catenin and FGF8, activation of Wnt target genes, and increased proliferation and horizontal expansion of neuroepithelial cells due to shortened cell-cycle length and decreased cell-cycle exit. Consistent with this phenotype, self-renewal of mutant neuroepithelial stem cells is enhanced in the... (More)
Regulating the choice between neural stem cell maintenance versus differentiation determines growth and size of the developing brain. Here we identify TGF-beta signaling as a crucial factor controlling these processes. At early developmental stages, TGF-beta signal activity is localized close to the ventricular surface of the neuroepithelium. In the midbrain, but not in the forebrain, Tgfbr2 ablation results in ectopic expression of Wnt1/beta-catenin and FGF8, activation of Wnt target genes, and increased proliferation and horizontal expansion of neuroepithelial cells due to shortened cell-cycle length and decreased cell-cycle exit. Consistent with this phenotype, self-renewal of mutant neuroepithelial stem cells is enhanced in the presence of FGF and requires Wnt signaling. Moreover, TGF-beta signal activation counteracts Wnt-incluced proliferation of midbrain neuroepithelial cells. Thus, TGF-beta signaling controls the size of a specific brain area, the dorsal midbrain, by antagonizing canonical Wnt signaling and negatively regulating self-renewal of neuroepithelial stem cells. (Less)
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type
Contribution to journal
publication status
published
subject
keywords
DEVBIO, STEMCELL
in
Cell Stem Cell
volume
2
issue
5
pages
472 - 483
publisher
Cell Press
external identifiers
  • wos:000255799300012
  • scopus:42649120343
ISSN
1934-5909
DOI
10.1016/j.stem.2008.03.006
language
English
LU publication?
yes
id
0e8f7907-8fc5-4345-91c3-33f89721da8c (old id 1204282)
date added to LUP
2008-09-17 12:52:39
date last changed
2017-07-23 03:47:39
@article{0e8f7907-8fc5-4345-91c3-33f89721da8c,
  abstract     = {Regulating the choice between neural stem cell maintenance versus differentiation determines growth and size of the developing brain. Here we identify TGF-beta signaling as a crucial factor controlling these processes. At early developmental stages, TGF-beta signal activity is localized close to the ventricular surface of the neuroepithelium. In the midbrain, but not in the forebrain, Tgfbr2 ablation results in ectopic expression of Wnt1/beta-catenin and FGF8, activation of Wnt target genes, and increased proliferation and horizontal expansion of neuroepithelial cells due to shortened cell-cycle length and decreased cell-cycle exit. Consistent with this phenotype, self-renewal of mutant neuroepithelial stem cells is enhanced in the presence of FGF and requires Wnt signaling. Moreover, TGF-beta signal activation counteracts Wnt-incluced proliferation of midbrain neuroepithelial cells. Thus, TGF-beta signaling controls the size of a specific brain area, the dorsal midbrain, by antagonizing canonical Wnt signaling and negatively regulating self-renewal of neuroepithelial stem cells.},
  author       = {Falk, Sven and Wurdak, Heiko and Ittner, Lars M and Ille, Fabian and Sumara, Grzegorz and Schmid, Marie-Theres and Draganova, Kalina and Lang, Karl S and Paratore, Christian and Levéen, Per and Suter, Ueli and Karlsson, Stefan and Born, Walter and Ricci, Romeo and Goetz, Magdalena and Sommer, Lukas},
  issn         = {1934-5909},
  keyword      = {DEVBIO,STEMCELL},
  language     = {eng},
  number       = {5},
  pages        = {472--483},
  publisher    = {Cell Press},
  series       = {Cell Stem Cell},
  title        = {Brain area-specific effect of TGF-beta signaling on Wnt-dependent neural stem cell expansion},
  url          = {http://dx.doi.org/10.1016/j.stem.2008.03.006},
  volume       = {2},
  year         = {2008},
}