腦是一個(gè)復(fù)雜的系統(tǒng),。在胚胎發(fā)育過程中,，大量的神經(jīng)細(xì)胞是依靠什么樣的機(jī)制來協(xié)調(diào)它們的運(yùn)動(dòng)遷移并排列組合成有序的組織結(jié)構(gòu)，一直吸引著研究者們濃厚的興趣,。4月19日,，國際生物學(xué)權(quán)威期刊《Cell》在線發(fā)表了中國科學(xué)院上海生命科學(xué)研究院神經(jīng)科學(xué)研究所在這一方面的一項(xiàng)新發(fā)現(xiàn)。
神經(jīng)科學(xué)研究所蒲慕明和袁小兵兩位研究員聯(lián)合指導(dǎo)的研究生管沉冰等經(jīng)過五年的潛心研究,，發(fā)現(xiàn)高度極性的神經(jīng)細(xì)胞在定向遷移過程中,，需要一種長距離的細(xì)胞內(nèi)信號(hào)傳遞過程，協(xié)調(diào)神經(jīng)細(xì)胞的不同部位對(duì)外界導(dǎo)向信號(hào)的反應(yīng),。他們觀察到,，遷移神經(jīng)細(xì)胞前方的生長錐是“偵查”前方信號(hào)的部位,，在自發(fā)遷移的神經(jīng)細(xì)胞前方遭遇排斥性的神經(jīng)導(dǎo)向因子Slit時(shí)會(huì)發(fā)生顯著的躲避反應(yīng)——生長錐首先 “撤退”，然后胞體停止前進(jìn),，并調(diào)轉(zhuǎn)方向,，最終細(xì)胞朝相反方向逃逸而去。在這個(gè)過程中,，會(huì)發(fā)生一個(gè)長距離的細(xì)胞內(nèi)鈣波“通訊”,，首先是Slit在生長錐內(nèi)“點(diǎn)燃”鈣離子“烽火”，緊接著是鈣離子“烽火”從生長錐傳遞到后方的胞體,，通知胞體前方的“敵情”,，進(jìn)而通過調(diào)節(jié)胞體部位的一種小分子GTP酶RhoA的活性和分布，使細(xì)胞體掉頭向后“撤退”,。正是這個(gè)鈣波信號(hào)協(xié)調(diào)了運(yùn)動(dòng)中的神經(jīng)細(xì)胞各部分對(duì)外界排斥性因子Slit的逃避反應(yīng),。目前已知多種發(fā)育性神經(jīng)系統(tǒng)疾病是由于神經(jīng)細(xì)胞遷移紊亂造成的,，患者常表現(xiàn)出智障,、癲癇等癥狀。因此,，對(duì)神經(jīng)細(xì)胞遷移導(dǎo)向基本機(jī)制的研究將有利于人們對(duì)這類發(fā)育性神經(jīng)系統(tǒng)疾病的認(rèn)識(shí)和防治,。
遷移的神經(jīng)元感受到外界的排斥性導(dǎo)向因子slit后發(fā)生遷移的反向過程示意圖
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原始出處:
Cell, Vol 129, 385-395, 20 April 2007
Article
Long-Range Ca2+ Signaling from Growth Cone to Soma Mediates Reversal of Neuronal Migration Induced by Slit-2
Chen-bing Guan,1,2 Hua-tai Xu,1 Ming Jin,1 Xiao-bing Yuan,1, and Mu-ming Poo1,3,
1 Institute of Neuroscience and Key Laboratory of Neurobiology, Shanghai Institute of Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
2 Graduate School of the Chinese Academy of Sciences, Shanghai, 200031, China
3 Division of Neurobiology, Department of Molecular and Cell Biology, Helen Wills Institute of Neuroscience, University of California, Berkeley, CA 94720-3200, USA
Corresponding author
Xiao-bing Yuan
[email protected]
Corresponding author
Mu-ming Poo
[email protected]
Neuronal migration and growth-cone extension are both guided by extracellular factors in the developing brain, but whether these two forms of guidance are mechanistically linked is unclear. Application of a Slit-2 gradient in front of the leading process of cultured cerebellar granule cells led to the collapse of the growth cone and the reversal of neuronal migration, an event preceded by a propagating Ca2+ wave from the growth cone to the soma. The Ca2+ wave was required for the Slit-2 effect and was sufficient by itself to induce the reversal of migration. The Slit-2-induced reversal of migration required active RhoA, which was accumulated at the front of the migrating neuron, and this polarized RhoA distribution was reversed during the migration reversal induced by either the Slit-2 gradient or the Ca2+ wave. Thus, long-range Ca2+ signaling coordinates the Slit-2-induced changes in motility at two distant parts of migrating neurons by regulating RhoA distribution.]
