Pujol Fabien, Kitabgi Patrick, Boudin Hélène
INSERM E0350, Hospital St Antoine, 184 rue du Fg St Antoine, 75571 Paris CEDEX 12, France.
J Cell Sci. 2005 Mar 1;118(Pt 5):1071-80. doi: 10.1242/jcs.01694.
Recent data have shown that the chemokine SDF-1 plays a critical role in several aspects of brain development such as cell migration and axon pathfinding. However, its potential function in the generation of axons and dendrites is poorly characterized. In order to better understand the role of SDF-1 in the development of central neurons, we studied the cellular distribution of the SDF-1 receptor CXCR4 by immunocytochemistry of developing hippocampal neurons and tested the effect of SDF-1 in process patterning at the early stages of neuronal development. We found that CXCR4 immunoreactivity undergoes a striking redistribution during development. At the early stages, from day 2 to day 4 in culture, CXCR4 is particularly concentrated at the leading edge of growing neurites. As the cells mature, staining declines at the tip of the processes and becomes more broadly distributed along axons and, to a lesser extent, dendrites. SDF-1 stimulation of neurons at day 1-2 in culture triggers several effects on neuronal morphogenesis. SDF-1 reduces growth cone number and axonal outgrowth but stimulates axonal branching. These latter two effects are not observed in other neurites. This study unravels a new role for SDF-1/CXCR4 in specifying hippocampal neuron morphology by regulating axonal patterning at an early stage of neuronal development.
最近的数据表明，趋化因子SDF-1在大脑发育的多个方面发挥着关键作用，如细胞迁移和轴突寻路。然而，其在轴突和树突生成中的潜在功能却鲜为人知。为了更好地理解SDF-1在中枢神经元发育中的作用，我们通过对发育中的海马神经元进行免疫细胞化学研究了SDF-1受体CXCR4的细胞分布，并测试了SDF-1在神经元发育早期对突起形成的影响。我们发现，CXCR4免疫反应性在发育过程中经历了显著的重新分布。在早期，即培养的第2天到第4天，CXCR4特别集中在生长神经突的前沿。随着细胞成熟，染色在突起尖端下降，并沿轴突更广泛地分布，在较小程度上也沿树突分布。在培养的第1-2天用SDF-1刺激神经元会对神经元形态发生产生多种影响。SDF-1减少生长锥数量和轴突生长，但刺激轴突分支。后两种效应在其他神经突中未观察到。这项研究揭示了SDF-1/CXCR4在神经元发育早期通过调节轴突模式来确定海马神经元形态方面的新作用。
