生物谷:Columbia大学医学中心科学家最近报道他们观测到了活体老鼠大脑组织中神经元干细胞的亚细胞行为细节。
观测到的结果发表在7月8日的《自然-神经学》(Nature Neuroscience)上,作者包括Jin-Wu Tsai,Helen Bremner和Richard Vallee,这为研究促使神经细胞移动的机制带来了帮助。医学中心将这一结果称为该方面迄今最详尽的信息,能帮助我们了解这一过程的失败为何将导致一系列严重的脑部问题。
CUMC细胞生物学和病理学教授Vallee认为这对于分析大脑疾病很有帮助,因为除了在大脑发育过程中起着重要作用外,神经元干细胞可能用于受损脑组织的修复。它们同样能用于分析脑肿瘤细胞的行为,从而带来新型脑癌化疗方法。
神经元干细胞位于发育中的大脑的脑室表层,它们通过大量连续的分裂循环来增生,以形成大脑皮层,这是大脑负责认知功能的区域。发育成的新细胞将向外移动一定距离,然后找到合适的区域来发育成大脑。细胞分裂过程的异常将导致大脑发育不良,俗称“大脑体积过小”,而移动过程异常将导致脑部没有足够的沟回,俗称“平滑大脑”。
为了直接观察以上脑部过程,Columbia大学博士生Tsai将DNA探针引入胚胎期的老鼠大脑中,这是一种目前越来越广泛用于脑发育研究的手段。利用RNA来抑制LIS1基因——这是最常见的引起大脑缺少沟回症状的基因,小组观测到了神经元干细胞的分裂以及移动被完全的阻止。 (教育部科技发展中心)
原文链接:http://www.physorg.com/news103386729.html
原始出处:
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 rv2025@columbia.edu
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.