The Oriented Emergence of Axons from Retinal Ganglion Cells Is Directed by Laminin Contact In Vivo
The Oriented Emergence of Axons from Retinal Ganglion Cells Is Directed by Laminin Contact In Vivo
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DOI：
10.1016/j.neuron.2011.03.013
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发表时间：
2011-04-28
期刊：
影响因子：
16.2
通讯作者：
Harris, William A.
中科院分区：
文献类型：
--
作者：
Randlett, Owen;Poggi, Lucia;Harris, William A.
神经发育过程中轴突出现的位置是如何确定的，目前尚不清楚。以往的研究对内在机制和外在机制的相对重要性意见不一。视网膜神经节细胞(RGCs)的轴突在体内基本形成，但由于RGCs是在极化的环境中从极化的神经上皮细胞发展而来的，因此区分内在和外在的影响是一个挑战。我们使用时间推移成像来证明层粘连蛋白直接作用于视网膜节细胞是必要和充分的，以在活体内定位轴突的出现。层粘连蛋白与新生视网膜节细胞的基底突起接触，阻止细胞进入随机的阶段2，引导早期轴突标志物Kif5c560-YFP的快速积累，并导致轴突生长锥的形成。这些结果表明，接触介导的线索可能对轴突出现的位置至关重要，并解释了在体外和体内观察到的细胞行为的差异。
How the site of axon emergence is specified during neural development is not understood. Previous studies disagree on the relative importance of intrinsic and extrinsic mechanisms. The axons of retinal ganglion cells (RGCs) emerge basally in vivo, yet because RGCs develop from polarized neuroepithelial cells within a polarized environment, disentangling intrinsic and extrinsic influences is a challenge. We use time-lapse imaging to demonstrate that Laminin acting directly on RGCs is necessary and sufficient to orient axon emergence in vivo. Laminin contact with the basal processes of newborn RGCs prevents the cells from entering a stochastic Stage 2 phase, directs the rapid accumulation of the early axonal marker Kif5c560-YFP, and leads to the formation of axonal growth cones. These results suggest that contact-mediated cues may be critical for the site of axon emergence and account for the differences in cellular behavior observed in vitro and in vivo.