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Falk, S.* ; Wurdak, H.* ; Ittner, L.M.* ; Ille, F.* ; Sumara, G.* ; Schmid, M.-T. ; Draganova, K.* ; Lang, K.S.* ; Paratore, C.* ; Leveen, P.* ; Suter, U.* ; Karlsson, S.* ; Born, W.* ; Ricci, R.* ; Götz, M. ; Sommer, L.*

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

Cell Stem Cell 2, 472-483 (2008)
DOI
Open Access Green as soon as Postprint is submitted to ZB.
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-induced 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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords DEVBIO; STEMCELL
Language english
Publication Year 2008
HGF-reported in Year 2008
ISSN (print) / ISBN 1934-5909
e-ISSN 1875-9777
Journal Cell Stem Cell
Quellenangaben Volume: 2, Issue: 5, Pages: 472-483 Article Number: , Supplement: ,
Publisher Cell Press
Publishing Place Cambridge, Mass.
Reviewing status Peer reviewed
Institute(s) Institute of Stem Cell Research (ISF)
POF-Topic(s) 30204 - Cell Programming and Repair
Research field(s) Stem Cell and Neuroscience
PSP Element(s) G-500800-001
DOI 10.1016/j.stem.2008.03.006
Scopus ID 42649120343
Erfassungsdatum 2008-08-21
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