（生物谷配圖 雜志封面圖片：經歷有絲分裂的神經上皮細胞的三維重建共聚焦圖像）
生物谷報道：歐洲科學家8日在《細胞—干細胞》上面發(fā)表論文稱TGF-β信號通路是控制神經干細胞分化的關鍵因素。
神經干細胞是一類多能干細胞,，可分化成各種神經元及神經膠質細胞。其分化會影響大腦的發(fā)育,。在神經干細胞發(fā)育的早期階段，TGF-β信號的活動主要位于接近神經上皮室表面的區(qū)域,。在中腦部份,，Tgfbr2消融將會造成Wnt1/β-catenin以及FGF8等信號因子的異常表達、Wnt目標基因的激活,、神經上皮細胞的橫向延伸和增生增強等,，形成延伸和增生的直接原因在于細胞周期長度的縮短以及細胞周期出口減少。而且,，變異的神經上皮干細胞的自我更新在FGF存在的情況下將得到增強,，并且這一增強需要Wnt信號。除此之外,，TGF-β信號的激活阻礙了Wnt誘導的中腦神經上皮細胞的增生,。因此研究人員認為，Wnt信號通過調控神經干細胞增殖和分化影響神經系統(tǒng)的生長發(fā)育,，而通過抵消Wnt信號,，同時負面調節(jié)神經上皮干細胞的自我更新過程，TGF-β信號控制著大腦一個特定區(qū)域—中腦背側的大小,。最后得出結論：神經干細胞的更新和擴張受到TGF-β和Wnt的共同調控。（生物谷www.bioon.com）
生物谷推薦原始出處：
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
[email protected]
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.
