Xu Hua-Tai, Yuan Xiao-bing, Guan Chen-bing, Duan Shumin, Wu Chien-ping, Feng Linyin
Institute of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China.
Proc Natl Acad Sci U S A. 2004 Mar 23;101(12):4296-301. doi: 10.1073/pnas.0303893101. Epub 2004 Mar 12.
Migration of neuronal precursor cells in the developing brain is guided by extracellular cues, but intracellular signaling processes underlying the guidance of neuronal migration are largely unknown. By examining the migration of cerebellar granule neurons along the surface of cocultured astroglial cells, we found that an extracellular gradient of Slit2, a chemorepellant for neuronal migration in vivo, caused a reversal in the direction of migration without affecting the migration speed. A Slit2 gradient elevated the intracellular concentration of Ca2+, probably due to calcium release from the internal store, led to a reversal of the preexisting asymmetric intracellular Ca2+ distribution in the soma of migrating neurons, and this reversal was closely related with its action of reversing the migrating direction. Asymmetric Ca2+ distribution in the soma was both necessary and sufficient for directing neuronal migration. These results have demonstrated an important role for Ca2+ in mediating neuronal responses to Slit2 and suggest a general mechanism for neuronal guidance.
发育中大脑内神经元前体细胞的迁移受细胞外信号的引导，但神经元迁移引导过程背后的细胞内信号传导过程很大程度上尚不清楚。通过检测小脑颗粒神经元沿共培养的星形胶质细胞表面的迁移，我们发现，Slit2（一种体内神经元迁移的化学排斥剂）的细胞外梯度会导致迁移方向逆转，而不影响迁移速度。Slit2梯度提高了细胞内Ca2+浓度，这可能是由于从内部储存库释放钙所致，导致迁移神经元胞体中先前存在的不对称细胞内Ca2+分布发生逆转，而这种逆转与其逆转迁移方向的作用密切相关。胞体中不对称的Ca2+分布对于引导神经元迁移既必要又充分。这些结果证明了Ca2+在介导神经元对Slit2的反应中的重要作用，并提示了一种神经元引导的一般机制。
