（生物谷配圖 雜志封面圖片：經(jīng)歷有絲分裂的神經(jīng)上皮細(xì)胞的三維重建共聚焦圖像）
生物谷報道：歐洲科學(xué)家8日在《細(xì)胞—干細(xì)胞》上面發(fā)表論文稱TGF-β信號通路是控制神經(jīng)干細(xì)胞分化的關(guān)鍵因素。
神經(jīng)干細(xì)胞是一類多能干細(xì)胞,，可分化成各種神經(jīng)元及神經(jīng)膠質(zhì)細(xì)胞,。其分化會影響大腦的發(fā)育,。在神經(jīng)干細(xì)胞發(fā)育的早期階段,，TGF-β信號的活動主要位于接近神經(jīng)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(dá),、Wnt目標(biāo)基因的激活,、神經(jīng)上皮細(xì)胞的橫向延伸和增生增強(qiáng)等,，形成延伸和增生的直接原因在于細(xì)胞周期長度的縮短以及細(xì)胞周期出口減少。而且,，變異的神經(jīng)上皮干細(xì)胞的自我更新在FGF存在的情況下將得到增強(qiáng),，并且這一增強(qiáng)需要Wnt信號。除此之外,，TGF-β信號的激活阻礙了Wnt誘導(dǎo)的中腦神經(jīng)上皮細(xì)胞的增生,。因此研究人員認(rèn)為，Wnt信號通過調(diào)控神經(jīng)干細(xì)胞增殖和分化影響神經(jīng)系統(tǒng)的生長發(fā)育,，而通過抵消Wnt信號,，同時負(fù)面調(diào)節(jié)神經(jīng)上皮干細(xì)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(cè)的大小,。最后得出結(jié)論：神經(jīng)干細(xì)胞的更新和擴(kuò)張受到TGF-β和Wnt的共同調(diào)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.
