Kirby Brandon B, Takada Norio, Latimer Andrew J, Shin Jimann, Carney Thomas J, Kelsh Robert N, Appel Bruce
Department of Biological Sciences, Vanderbilt University, 465 21st Avenue South, Nashville, Tennessee 37232, USA.
Nat Neurosci. 2006 Dec;9(12):1506-11. doi: 10.1038/nn1803. Epub 2006 Nov 12.
Myelinating oligodendrocytes arise from migratory and proliferative oligodendrocyte progenitor cells (OPCs). Complete myelination requires that oligodendrocytes be uniformly distributed and form numerous, periodically spaced membrane sheaths along the entire length of target axons. Mechanisms that determine spacing of oligodendrocytes and their myelinating processes are not known. Using in vivo time-lapse confocal microscopy, we show that zebrafish OPCs continuously extend and retract numerous filopodium-like processes as they migrate and settle into their final positions. Process remodeling and migration paths are highly variable and seem to be influenced by contact with neighboring OPCs. After laser ablation of oligodendrocyte-lineage cells, nearby OPCs divide more frequently, orient processes toward the ablated cells and migrate to fill the unoccupied space. Thus, process activity before axon wrapping might serve as a surveillance mechanism by which OPCs determine the presence or absence of nearby oligodendrocyte-lineage cells, facilitating uniform spacing of oligodendrocytes and complete myelination.
形成髓鞘的少突胶质细胞源自迁移性和增殖性少突胶质前体细胞(OPC)。完全髓鞘形成要求少突胶质细胞均匀分布,并沿着靶轴突的全长形成众多周期性间隔的膜鞘。决定少突胶质细胞及其髓鞘形成过程间距的机制尚不清楚。利用体内延时共聚焦显微镜,我们发现斑马鱼OPC在迁移并定居到最终位置时,会不断伸出和缩回众多丝状伪足样突起。突起重塑和迁移路径高度可变,似乎受到与相邻OPC接触的影响。在对少突胶质细胞谱系细胞进行激光消融后,附近的OPC更频繁地分裂,将突起朝向消融细胞的方向,并迁移以填补未占据的空间。因此,轴突包裹前的突起活动可能作为一种监测机制,通过该机制OPC确定附近少突胶质细胞谱系细胞的存在与否,促进少突胶质细胞的均匀间距和完全髓鞘形成。