| Literature DB >> 18462697 |
Sven Falk1, Heiko Wurdak, Lars M Ittner, Fabian Ille, Grzegorz Sumara, Marie-Theres Schmid, Kalina Draganova, Karl S Lang, Christian Paratore, Per Leveen, Ueli Suter, Stefan Karlsson, Walter Born, Romeo Ricci, Magdalena Götz, Lukas Sommer.
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-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.Entities:
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Year: 2008 PMID： 18462697 DOI： 10.1016/j.stem.2008.03.006
Source DB: PubMed Journal: Cell Stem Cell ISSN： 1875-9777 Impact factor: 24.633