生物谷报道：最近，我国科研人员发现一种梯度表达的分泌性导向分子指引了大脑皮层神经元的放射状迁移。这一发现有助于人们更好地理解高度有序的大脑皮层结构是如何形成的，从而为研究脑发育障碍和疾病提供了新的思路和途径。
这一由中国科学院神经科学研究所研究人员的研究成果已经发表在最近出版的国际学术期刊《自然·神经科学》上。
大脑皮层神经元迁移的调节机制是发育神经生物学中尚未解决的重大问题。通常认为，新生的锥体神经元从生发区向皮层上层的迁移，依赖于放射状胶质纤维的导引。而且，大脑皮层板层结构的形成受迁移神经元与胶质纤维的黏附及脱离机制所影响。长久以来，人们一直忽略了另一种潜在的调节机制，即分泌性分子的浓度梯度用于指导皮层神经元的放射状迁移。
中国科学院神经科学研究所研究人员陈罡、司马健和金明等采用“在体子宫内基因电转技术”，可长程观察一群皮层神经元在体内的迁移。他们发现，体内通过阻断分泌性导向分子Semaphorin-3A的信号，可以导致迁移的停滞，并伴随神经元伸展方向的错乱。体外实验也发现，内源性Semaphorin-3A的浓度梯度对于新生神经元的正确迁移是必须的，并且起吸引性导向作用。
这些研究证明了神经元的放射状迁移受胞外导向分子的指引。这种迁移的趋化性导向假说，有助于人们更好地理解高度有序的皮层结构是如何形成的，从而为研究脑发育障碍和疾病提供了新的思路和途径。
记者了解到，这项研究工作得到了中国科学院、科技部、国家自然科学基金委员会及上海市科委的资助。（生物谷援引新华网）
生物谷推荐原始出处：
Nature Neuroscience 11, 36 - 44 (2007)
Published online: 2 December 2007 | Corrected online: 9 December 2007 | doi:10.1038/nn2018
Semaphorin-3A guides radial migration of cortical neurons during development
Gang Chen1,2,3, Jian Sima1,2,3, Ming Jin1,3, Kai-yu Wang1,2, Xiao-jing Xue1,2, Wang Zheng1,2, Yu-qiang Ding1 & Xiao-bing Yuan1
Abstract
Postmitotic neurons in the developing cortex migrate along radial glial fibers to their proper location in the cortical plate and form the layered structure. Here we report that the radial migration of rat layer II/III cortical neurons requires guidance by the extracellular diffusible factor Semaphorin-3A (Sema3A). This factor is expressed in a descending gradient across the cortical layers, whereas its receptor neuropilin-1 (NP1) is highly expressed in migrating neurons. Downregulation or conditional knockout of NP1 in newborn cortical neurons impedes their radial migration by disrupting their radial orientation during migration without altering their cell fate. Studies in cultured cortical slices further show that the endogenous gradient of Sema3A is required for the proper migration of newborn neurons. In addition, transwell chemotaxis assays show that isolated newborn neurons are attracted by Sema3A. Thus, Sema3A may function as a chemoattractive guidance signal for the radial migration of newborn cortical neurons toward upper layers.
Institute of Neuroscience and Key State Laboratory of Neurobiology, Shanghai Institute for Biological Sciences, 320 Yue Yang Road, Shanghai 200031, China.
Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China.
These authors contributed equally to this work.
Correspondence to: Xiao-bing Yuan1 e-mail: yuanxb@ion.ac.cn
