Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-12024
Falk , S; Wurdak, H; Ittner, L M; Ille, F; Sumara, G; Schmid, M T; Draganova, K; Lang, K S; Paratore, C; Schwerdtfeger, K; Leveen, P; Suter, U; Karlsson, S; Born, W; Ricci, R; Gotz, M; Sommer, L (2008). Brain area-specific effect of TGF-beta signaling on Wnt-dependent neural stem cell expansion. Cell Stem Cell, 2(5):472-482.
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.
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > Institute of Anatomy|
|DDC:||570 Life sciences; biology|
610 Medicine & health
|Deposited On:||03 Feb 2009 11:06|
|Last Modified:||27 Nov 2013 21:31|
|Citations:||Web of Science®. Times cited: 50|
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