（生物谷配图 杂志封面图片：经历有丝分裂的神经上皮细胞的三维重建共聚焦图像）
生物谷报道：欧洲科学家8日在《细胞—干细胞》上面发表论文称TGF-β信号通路是控制神经干细胞分化的关键因素。
神经干细胞是一类多能干细胞，可分化成各种神经元及神经胶质细胞。其分化会影响大脑的发育。在神经干细胞发育的早期阶段，TGF-β信号的活动主要位于接近神经上皮室表面的区域。在中脑部份，Tgfbr2消融将会造成Wnt1/β-catenin以及FGF8等信号因子的异常表达、Wnt目标基因的激活、神经上皮细胞的横向延伸和增生增强等，形成延伸和增生的直接原因在于细胞周期长度的缩短以及细胞周期出口减少。而且，变异的神经上皮干细胞的自我更新在FGF存在的情况下将得到增强，并且这一增强需要Wnt信号。除此之外，TGF-β信号的激活阻碍了Wnt诱导的中脑神经上皮细胞的增生。因此研究人员认为，Wnt信号通过调控神经干细胞增殖和分化影响神经系统的生长发育，而通过抵消Wnt信号，同时负面调节神经上皮干细胞的自我更新过程，TGF-β信号控制着大脑一个特定区域—中脑背侧的大小。最后得出结论：神经干细胞的更新和扩张受到TGF-β和Wnt的共同调控。（生物谷www.bioon.com）
生物谷推荐原始出处：
Cell Stem Cell，Vol 2, 472-483, 08 May 2008，Sven Falk, Lukas Sommer
Brain Area-Specific Effect of TGF-β Signaling on Wnt-Dependent Neural Stem Cell Expansion
Sven Falk,1,9,10 Heiko Wurdak,1,9,11 Lars M. Ittner,2,12 Fabian Ille,1 Grzegorz Sumara,1 Marie-Theres Schmid,3 Kalina Draganova,10 Karl S. Lang,6 Christian Paratore,1 Per Leveen,7,8 Ueli Suter,1 Stefan Karlsson,7,8 Walter Born,2 Romeo Ricci,1 Magdalena Götz,3,4,5 and Lukas Sommer1,10,
1 Institute of Cell Biology, ETH-Hönggerberg, CH-8093 Zurich, Switzerland
2 Orthopedic University Hospital Balgrist, CH-8008 Zurich, Switzerland
3 Institute of Stem Cell Research, HelmholtzZentrum Munchen, National Research, Center for Environmental Health, D-85764 Neuherberg/Munich, Germany
4 Physiological Genomics, University of Munich, D-80633 Munich, Germany
5 Center for Integrated Protein Science Munich, D-80633 Munich, Germany
6 Institute of Experimental Immunology, University Hospital Zurich, CH-8091 Zurich, Switzerland
7 Department of Molecular Medicine and Gene Therapy, Lund University, S-22184 Lund, Sweden
8 Department of Cell and Molecular Biology, Lund University, S-22184 Lund, Sweden
Corresponding author
Lukas Sommer
lukas.sommer@anatom.uzh.ch
Summary
Regulating the choice between neural stem cell maintenance versus differentiation determines growth and size of the developing brain. Here we identify TGF-β signaling as a crucial factor controlling these processes. At early developmental stages, TGF-β 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/β-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-β signal activation counteracts Wnt-induced proliferation of midbrain neuroepithelial cells. Thus, TGF-β 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.
