Fox Michael A, Afshari Fatemah S, Alexander John K, Colello Raymond J, Fuss Babette
Department of Anatomy and Neurobiology, Virginia Commonwealth University School of Medicine, Richmond, Virginia 23298, USA.
Glia. 2006 Apr 1;53(5):563-6. doi: 10.1002/glia.20293.
During development, postmigratory, premyelinating oligodendrocytes extend processes that navigate through the central nervous system (CNS) environment, where they recognize a number of extracellular cues, including axonal segments to be myelinated. Ultimately this recognition event leads to the formation of the CNS myelin sheath. However, the morphological structures and molecular mechanisms that control such oligodendroglial pathfinding are poorly understood. Here we show that postmigratory, premyelinating oligodendrocyte processes possess at their distal tips expansions that ultrastructurally resemble growth cones of postmigratory neurons and that we will refer to as OLG-growth cones. OLG-growth cones are highly motile and capable of mediating process outgrowth, retraction, and branching. In addition, they express regulators of cytoskeletal organization, GAP43 and cofilin, that are known to mediate neuronal growth cone navigation. In a choice situation, processes of postmigratory, premyelinating oligodendrocytes and their OLG-growth cones have the ability to selectively avoid a nonpermissive substrate, that is, collagen IV. Thus, our findings provide, for the first time, a detailed characterization of sensorimotor structures present at the tips of postmigratory, premyelinating oligodendrocyte processes. Furthermore, the data presented here suggest that, although the cellular mechanisms involved in growth cone steering may be similar for postmigratory neuronal and oligodendroglial cells, extracellular cues may be interpreted in a cell-type-specific fashion.
在发育过程中,迁移后、髓鞘形成前的少突胶质细胞伸出突起,这些突起在中枢神经系统(CNS)环境中穿行,在该环境中它们识别多种细胞外信号,包括即将被髓鞘化的轴突段。最终,这种识别事件导致中枢神经系统髓鞘的形成。然而,控制这种少突胶质细胞寻路的形态结构和分子机制却知之甚少。在这里,我们表明迁移后、髓鞘形成前的少突胶质细胞突起在其远端具有膨大结构,这些结构在超微结构上类似于迁移后神经元的生长锥,我们将其称为少突胶质细胞生长锥。少突胶质细胞生长锥具有高度的运动性,能够介导突起的生长、回缩和分支。此外,它们表达细胞骨架组织调节因子GAP43和丝切蛋白,已知这些因子可介导神经元生长锥的导航。在选择情境中,迁移后、髓鞘形成前的少突胶质细胞及其少突胶质细胞生长锥的突起能够选择性地避开非允许性底物,即IV型胶原。因此,我们的研究结果首次详细描述了迁移后、髓鞘形成前的少突胶质细胞突起尖端存在的感觉运动结构。此外,这里呈现的数据表明,尽管迁移后神经元和少突胶质细胞中参与生长锥导向的细胞机制可能相似,但细胞外信号可能以细胞类型特异性的方式被解读。