UNIQUE CHANGES OF GANGLION-CELL GROWTH CONE BEHAVIOR FOLLOWING CELL-ADHESION MOLECULE PERTURBATIONS - A TIME-LAPSE STUDY OF THE LIVING RETINA

UNIQUE CHANGES OF GANGLION-CELL GROWTH CONE BEHAVIOR FOLLOWING CELL-ADHESION MOLECULE PERTURBATIONS - A TIME-LAPSE STUDY OF THE LIVING RETINA
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DOI:
10.1006/mcne.1995.1032
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发表时间:
1995-10-01
影响因子:
3.5
通讯作者:
SILVER, J
SILVER, J
中科院分区:
医学3区
文献类型:
--
作者:
BRITTIS, PA;LEMMON, V;SILVER, J

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在哺乳动物视网膜中,引导视网膜神经节细胞轴突到达视裂隙的机制多种多样。在本研究中,我们使用延时视频显微镜显示,在视网膜神经上皮的中心,生长锥使用先前形成的轴突支架作为基质进行引导。中视网膜正常生长锥的高倍延时视频显微镜显示,它们具有改变形状的能力,从拥抱其他轴突的长流线型形状转变为更扁平的形状,在轴突或神经上皮端足之间移动。在对这些事件中特定细胞相互作用作用的研究中,针对L1和NCAM的Fab片段,单独或联合使用,都被发现对视网膜神经节细胞生长锥有显著而独特的影响。Anti-L1 Fab片段严重破坏了径向生长锥的取向和生长速率。抗1处理的生长球果最初停滞2小时,然后改变方向,此后恢复延伸率是对照制剂的两倍。相反,anti-NCAM Fab不会影响生长锥的方向,但会导致生长锥的亚群开始加速,然后急剧增大,停滞,最终停止。这些结果表明,L1和NCAM在轴突生长的促进和方向上发挥着不同的作用,并与排斥分子和物理通道一起,为视网膜轴突向视裂隙的单向生长提供了重要信息。
In the mammalian retina, multiple mechanisms are responsible for guiding retinal ganglion cell axons to the optic fissure. In the present study we have used time-lapse videomicroscopy to show that, within the center of the retinal neuroepithelium, growth cones use a scaffold of previously formed axons as a substrate for guidance. High magnification time-lapse videomicroscopy of normal growth cones in the midretina have shown that they have the ability to alter their shape from long, streamlined forms that hug other axons to more flattened forms that move between axons or neuroepithelial endfeet. In studies on the role of specific cell interactions in these events, Fab fragments against L1 and NCAM, administered either alone or in combination, were found to have dramatic and distinct effects on retinal ganglion cell growth cones. Anti-L1 Fab fragments severely disrupted radial growth cone orientation and rate of outgrowth. The anti-1-treated growth cones initially stalled for 2 h, then changed direction and, thereafter, resumed an elongation rate twice as fast as in control preparations. By contrast, anti-NCAM Fab did not affect growth cone direction, but caused subsets of growth cones to speed up initially, then to dramatically increase in size, stall, and eventually halt. These results imply that L1 and NCAM play different roles in the promotion and direction of axon growth and, along with repulsive molecules and physical channels, provide essential information for the unidirectional growth of retinal axons into the optic fissure.