Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3DY, UK.
Neuron. 2011 Apr 28;70(2):266-80. doi: 10.1016/j.neuron.2011.03.013.
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.
神经发育过程中轴突起始位置是如何确定的目前还不清楚。先前的研究对内在和外在机制的相对重要性存在分歧。视网膜神经节细胞(RGC)的轴突在体内基底处出现,但由于 RGC 是从极化神经上皮细胞在极化环境中发育而来的,因此要理清内在和外在影响是一项挑战。我们使用延时成像技术证明,层粘连蛋白直接作用于 RGC 对于体内轴突起始的定向是必要且充分的。层粘连蛋白与新生 RGC 基底过程的接触可防止细胞进入随机的第 2 阶段,指导早期轴突标志物 Kif5c560-YFP 的快速积累,并导致轴突生长锥的形成。这些结果表明,接触介导的线索对于轴突起始的位置可能是至关重要的,并解释了在体外和体内观察到的细胞行为的差异。