生物谷報道:最近,,我國科研人員發(fā)現(xiàn)一種梯度表達(dá)的分泌性導(dǎo)向分子指引了大腦皮層神經(jīng)元的放射狀遷移,。這一發(fā)現(xiàn)有助于人們更好地理解高度有序的大腦皮層結(jié)構(gòu)是如何形成的,從而為研究腦發(fā)育障礙和疾病提供了新的思路和途徑,。
這一由中國科學(xué)院神經(jīng)科學(xué)研究所研究人員的研究成果已經(jīng)發(fā)表在最近出版的國際學(xué)術(shù)期刊《自然·神經(jīng)科學(xué)》上,。
大腦皮層神經(jīng)元遷移的調(diào)節(jié)機(jī)制是發(fā)育神經(jīng)生物學(xué)中尚未解決的重大問題。通常認(rèn)為,,新生的錐體神經(jīng)元從生發(fā)區(qū)向皮層上層的遷移,,依賴于放射狀膠質(zhì)纖維的導(dǎo)引。而且,,大腦皮層板層結(jié)構(gòu)的形成受遷移神經(jīng)元與膠質(zhì)纖維的黏附及脫離機(jī)制所影響,。長久以來,人們一直忽略了另一種潛在的調(diào)節(jié)機(jī)制,,即分泌性分子的濃度梯度用于指導(dǎo)皮層神經(jīng)元的放射狀遷移,。
中國科學(xué)院神經(jīng)科學(xué)研究所研究人員陳罡、司馬健和金明等采用“在體子宮內(nèi)基因電轉(zhuǎn)技術(shù)”,,可長程觀察一群皮層神經(jīng)元在體內(nèi)的遷移,。他們發(fā)現(xiàn),,體內(nèi)通過阻斷分泌性導(dǎo)向分子Semaphorin-3A的信號,,可以導(dǎo)致遷移的停滯,,并伴隨神經(jīng)元伸展方向的錯亂。體外實驗也發(fā)現(xiàn),,內(nèi)源性Semaphorin-3A的濃度梯度對于新生神經(jīng)元的正確遷移是必須的,,并且起吸引性導(dǎo)向作用。
這些研究證明了神經(jīng)元的放射狀遷移受胞外導(dǎo)向分子的指引,。這種遷移的趨化性導(dǎo)向假說,,有助于人們更好地理解高度有序的皮層結(jié)構(gòu)是如何形成的,從而為研究腦發(fā)育障礙和疾病提供了新的思路和途徑,。
記者了解到,,這項研究工作得到了中國科學(xué)院、科技部,、國家自然科學(xué)基金委員會及上海市科委的資助,。(生物谷援引新華網(wǎng))
生物谷推薦原始出處:
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: [email protected]