Department of Molecular Cell and Developmental Biology, University of California, Los Angeles, CA 90095, USA.
Curr Biol. 2009 Dec 29;19(24):2086-90. doi: 10.1016/j.cub.2009.10.051. Epub 2009 Dec 3.
The structural plasticity of neurites in the central nervous system (CNS) diminishes dramatically after initial development, but the peripheral nervous system (PNS) retains substantial plasticity into adulthood. Nevertheless, functional reinnervation by injured peripheral sensory neurons is often incomplete [1-6]. To investigate the developmental control of skin reinnervation, we imaged the regeneration of trigeminal sensory axon terminals in live zebrafish larvae following laser axotomy. When axons were injured during early stages of outgrowth, regenerating and uninjured axons grew into denervated skin and competed with one another for territory. At later stages, after the establishment of peripheral arbor territories, the ability of uninjured neighbors to sprout diminished severely, and although injured axons reinitiated growth, they were repelled by denervated skin. Regenerating axons were repelled specifically by their former territories, suggesting that local inhibitory factors persist in these regions. Antagonizing the function of several members of the Nogo receptor (NgR)/RhoA pathway improved the capacity of injured axons to grow into denervated skin. Thus, as in the CNS, impediments to reinnervation in the PNS arise after initial establishment of axon arbor structure.
中枢神经系统(CNS)的神经突的结构可塑性在初始发育后显著降低,但周围神经系统(PNS)在成年期仍保持相当大的可塑性。然而,受伤的周围感觉神经元的功能再支配常常是不完全的[1-6]。为了研究皮肤再支配的发育控制,我们在活体斑马鱼幼虫中对三叉神经感觉轴突末梢的再生进行了成像,方法是激光切断轴突。当轴突在生长早期受伤时,再生和未受伤的轴突会长入去神经的皮肤,并相互竞争领地。在后期,在建立了外周树突区之后,未受伤的邻居的发芽能力严重下降,尽管受伤的轴突重新开始生长,但它们被去神经的皮肤排斥。再生轴突被它们以前的领地特异性排斥,这表明这些区域内持续存在局部抑制因子。拮抗几种神经生长抑制因子受体(NgR)/RhoA 通路成员的功能,可提高受伤轴突长入去神经皮肤的能力。因此,与中枢神经系统一样,PNS 中的再支配障碍是在轴突树突结构初始建立之后出现的。