生物谷:Columbia大學醫(yī)學中心科學家最近報道他們觀測到了活體老鼠大腦組織中神經(jīng)元干細胞的亞細胞行為細節(jié),。
觀測到的結(jié)果發(fā)表在7月8日的《自然-神經(jīng)學》(Nature Neuroscience)上,作者包括Jin-Wu Tsai,,Helen Bremner和Richard Vallee,這為研究促使神經(jīng)細胞移動的機制帶來了幫助,。醫(yī)學中心將這一結(jié)果稱為該方面迄今最詳盡的信息,,能幫助我們了解這一過程的失敗為何將導致一系列嚴重的腦部問題。
CUMC細胞生物學和病理學教授Vallee認為這對于分析大腦疾病很有幫助,,因為除了在大腦發(fā)育過程中起著重要作用外,,神經(jīng)元干細胞可能用于受損腦組織的修復。它們同樣能用于分析腦腫瘤細胞的行為,,從而帶來新型腦癌化療方法,。
神經(jīng)元干細胞位于發(fā)育中的大腦的腦室表層,它們通過大量連續(xù)的分裂循環(huán)來增生,,以形成大腦皮層,,這是大腦負責認知功能的區(qū)域。發(fā)育成的新細胞將向外移動一定距離,,然后找到合適的區(qū)域來發(fā)育成大腦,。細胞分裂過程的異常將導致大腦發(fā)育不良,俗稱“大腦體積過小”,,而移動過程異常將導致腦部沒有足夠的溝回,,俗稱“平滑大腦”。
為了直接觀察以上腦部過程,,Columbia大學博士生Tsai將DNA探針引入胚胎期的老鼠大腦中,,這是一種目前越來越廣泛用于腦發(fā)育研究的手段。利用RNA來抑制LIS1基因——這是最常見的引起大腦缺少溝回癥狀的基因,,小組觀測到了神經(jīng)元干細胞的分裂以及移動被完全的阻止,。 (教育部科技發(fā)展中心)
原文鏈接:http://www.physorg.com/news103386729.html
原始出處:
Nature Neuroscience
Published online: 8 July 2007; | doi:10.1038/nn1934
Dual subcellular roles for LIS1 and dynein in radial neuronal migration in live brain tissue
Jin-Wu Tsai1, K Helen Bremner2 & Richard B Vallee2
1 Integrated Program in Cellular, Molecular and Biophysical Studies, Columbia University, 630 W 168th Street, New York, New York 10032, USA.
2 Department of Pathology and Cell Biology. Columbia University, 630 W 168th Street, New York, New York 10032, USA.
3 Center for Neurobiology and Behavior, College of Physicians and Surgeons, Columbia University, 630 W 168th Street, New York, New York 10032, USA.
Correspondence should be addressed to Richard B Vallee [email protected]
During brain development, neural precursor cells migrate along radial glial fibers to populate the neocortex. RNA interference (RNAi) of the lissencephaly gene LIS1 (also known as PAFAH1b1) inhibits somal movement but not process extension of neural precursors in live brain slices. Here we report imaging of the subcellular events accompanying neural precursor migration and the effects of LIS1, cytoplasmic dynein and myosin II inhibition. Centrosomes move continuously and often far in advance of nuclei, which show extreme saltatory behavior. LIS1 and dynein RNAi inhibit centrosomal and nuclear movement independently, whereas myosin II inhibition blocks only nuclear translocation. Imaging of the microtubule end-binding protein 3 (EB3) reveals a centrosome-centered array of microtubules in live neural precursors under all conditions examined. Dynein is concentrated both at a swelling in the leading process reported to initiate each migratory cycle and in the soma. Thus, dynein pulls on the microtubule network from the swelling. The nucleus is transported along the trailing microtubules by dynein assisted by myosin II.