脑是一个复杂的系统。在胚胎发育过程中，大量的神经细胞是依靠什么样的机制来协调它们的运动迁移并排列组合成有序的组织结构，一直吸引着研究者们浓厚的兴趣。4月19日，国际生物学权威期刊《Cell》在线发表了中国科学院上海生命科学研究院神经科学研究所在这一方面的一项新发现。
神经科学研究所蒲慕明和袁小兵两位研究员联合指导的研究生管沉冰等经过五年的潜心研究，发现高度极性的神经细胞在定向迁移过程中，需要一种长距离的细胞内信号传递过程，协调神经细胞的不同部位对外界导向信号的反应。他们观察到，迁移神经细胞前方的生长锥是“侦查”前方信号的部位，在自发迁移的神经细胞前方遭遇排斥性的神经导向因子Slit时会发生显著的躲避反应——生长锥首先 “撤退”，然后胞体停止前进，并调转方向，最终细胞朝相反方向逃逸而去。在这个过程中，会发生一个长距离的细胞内钙波“通讯”，首先是Slit在生长锥内“点燃”钙离子“烽火”，紧接着是钙离子“烽火”从生长锥传递到后方的胞体，通知胞体前方的“敌情”，进而通过调节胞体部位的一种小分子GTP酶RhoA的活性和分布，使细胞体掉头向后“撤退”。正是这个钙波信号协调了运动中的神经细胞各部分对外界排斥性因子Slit的逃避反应。目前已知多种发育性神经系统疾病是由于神经细胞迁移紊乱造成的，患者常表现出智障、癫痫等症状。因此，对神经细胞迁移导向基本机制的研究将有利于人们对这类发育性神经系统疾病的认识和防治。
迁移的神经元感受到外界的排斥性导向因子slit后发生迁移的反向过程示意图
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原始出处:
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
yuanxb@ion.ac.cn
Corresponding author
Mu-ming Poo
mpoo@berkeley.edu
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.]
