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

被引：112

作者：

Falk, Sven ^{[8
]}

Wurdak, Heiko ^{[8
]}

Ittner, Lars M. ^{[1
]}

Ille, Fabian ^{[8
]}

Sumara, Grzegorz ^{[8
]}

Schmid, Marie-Theres ^{[2
]}

Draganova, Kalina

Lang, Karl S. ^{[5
]}

Paratore, Christian ^{[8
]}

Leveen, Per ^{[6
,7
]}

Suter, Ueli ^{[8
]}

Karlsson, Stefan ^{[6
,7
]}

Born, Walter ^{[1
]}

Ricci, Romeo ^{[8
]}

Goetz, Magdalena ^{[2
,3
,4
]}

Sommer, Lukas ^{[8
]}

机构：

[1] Orthoped Univ, Hosp Balgrist, CH-8008 Zurich, Switzerland

[2] Natl Res Ctr Environm Hlth, HelmholtzZentrum Munchen, Inst Stem Cell Res, D-85764 Neuherberg, Germany

[3] Univ Munich, D-80539 Munich, Germany

[4] Ctr Integrated Prot Sci Munich, D-80633 Munich, Germany

[5] Univ Zurich Hosp, Inst Expt Immunol, CH-8091 Zurich, Switzerland

[6] Lund Univ, Dept Mol Med & Gene Therapy, S-22184 Lund, Sweden

[7] Lund Univ, Dept Cell & Mol Biol, S-22184 Lund, Sweden

[8] ETH Honggerberg, Inst Cell Biol, CH-8093 Zurich, Switzerland

来源：

CELL STEM CELL | 2008年 / 2卷 / 05期

关键词：

D O I：

10.1016/j.stem.2008.03.006

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

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.

引用

页码：472 / 483

页数：12

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